JP6120819B2 - 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 - Google Patents
癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 Download PDFInfo
- Publication number
- JP6120819B2 JP6120819B2 JP2014186846A JP2014186846A JP6120819B2 JP 6120819 B2 JP6120819 B2 JP 6120819B2 JP 2014186846 A JP2014186846 A JP 2014186846A JP 2014186846 A JP2014186846 A JP 2014186846A JP 6120819 B2 JP6120819 B2 JP 6120819B2
- Authority
- JP
- Japan
- Prior art keywords
- binding protein
- antigen
- psca
- antigen binding
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 84
- 102100036735 Prostate stem cell antigen Human genes 0.000 title claims description 53
- 201000011510 cancer Diseases 0.000 title claims description 38
- 238000001514 detection method Methods 0.000 title claims description 10
- 230000008685 targeting Effects 0.000 title description 20
- 239000000427 antigen Substances 0.000 title description 19
- 108091007433 antigens Proteins 0.000 title description 19
- 102000036639 antigens Human genes 0.000 title description 19
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 title description 3
- 210000000130 stem cell Anatomy 0.000 title description 3
- 230000001826 anti-prostatic effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims description 53
- 101710120463 Prostate stem cell antigen Proteins 0.000 claims description 52
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 210000004027 cell Anatomy 0.000 claims description 44
- 238000003384 imaging method Methods 0.000 claims description 40
- 235000018102 proteins Nutrition 0.000 claims description 35
- 102000004169 proteins and genes Human genes 0.000 claims description 35
- 102000025171 antigen binding proteins Human genes 0.000 claims description 34
- 108091000831 antigen binding proteins Proteins 0.000 claims description 34
- 235000001014 amino acid Nutrition 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 27
- 150000001413 amino acids Chemical group 0.000 claims description 24
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 23
- 206010060862 Prostate cancer Diseases 0.000 claims description 22
- 238000001727 in vivo Methods 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 19
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 17
- 210000002307 prostate Anatomy 0.000 claims description 17
- 201000002528 pancreatic cancer Diseases 0.000 claims description 16
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 15
- 229940079593 drug Drugs 0.000 claims description 14
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 14
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 12
- 206010005003 Bladder cancer Diseases 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 11
- 102000004190 Enzymes Human genes 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 10
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 claims description 9
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 9
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 239000003550 marker Substances 0.000 claims description 7
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 6
- 239000002254 cytotoxic agent Substances 0.000 claims description 6
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 6
- 238000002600 positron emission tomography Methods 0.000 claims description 6
- 238000001959 radiotherapy Methods 0.000 claims description 6
- 229960003048 vinblastine Drugs 0.000 claims description 6
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 6
- 108010092160 Dactinomycin Proteins 0.000 claims description 5
- 239000004472 Lysine Substances 0.000 claims description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 5
- 229930012538 Paclitaxel Natural products 0.000 claims description 5
- 108010039491 Ricin Proteins 0.000 claims description 5
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 5
- 229960000640 dactinomycin Drugs 0.000 claims description 5
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 5
- 229960005420 etoposide Drugs 0.000 claims description 5
- 229940088597 hormone Drugs 0.000 claims description 5
- 239000005556 hormone Substances 0.000 claims description 5
- 229960001592 paclitaxel Drugs 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 5
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 4
- 108010066676 Abrin Proteins 0.000 claims description 4
- 229930192392 Mitomycin Natural products 0.000 claims description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
- 238000005481 NMR spectroscopy Methods 0.000 claims description 4
- 239000002738 chelating agent Substances 0.000 claims description 4
- 229960001338 colchicine Drugs 0.000 claims description 4
- 238000002591 computed tomography Methods 0.000 claims description 4
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 4
- 229960000975 daunorubicin Drugs 0.000 claims description 4
- 229960004679 doxorubicin Drugs 0.000 claims description 4
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 claims description 4
- 229960005542 ethidium bromide Drugs 0.000 claims description 4
- 239000007850 fluorescent dye Substances 0.000 claims description 4
- 239000003862 glucocorticoid Substances 0.000 claims description 4
- 229960004857 mitomycin Drugs 0.000 claims description 4
- 238000012634 optical imaging Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 4
- 229960001278 teniposide Drugs 0.000 claims description 4
- 229960004528 vincristine Drugs 0.000 claims description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 4
- 108010053187 Diphtheria Toxin Proteins 0.000 claims description 3
- 102000016607 Diphtheria Toxin Human genes 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- 230000001472 cytotoxic effect Effects 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000002603 single-photon emission computed tomography Methods 0.000 claims description 3
- FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-UHFFFAOYSA-N 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 claims description 2
- 238000010317 ablation therapy Methods 0.000 claims description 2
- 108010001818 alpha-sarcin Proteins 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 230000029918 bioluminescence Effects 0.000 claims description 2
- 238000005415 bioluminescence Methods 0.000 claims description 2
- 229930195731 calicheamicin Natural products 0.000 claims description 2
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 claims description 2
- 231100000433 cytotoxic Toxicity 0.000 claims description 2
- 108010028531 enomycin Proteins 0.000 claims description 2
- 239000003667 hormone antagonist Substances 0.000 claims description 2
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 108010076042 phenomycin Proteins 0.000 claims description 2
- 238000012636 positron electron tomography Methods 0.000 claims description 2
- RTIXKCRFFJGDFG-UHFFFAOYSA-N chrysin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 RTIXKCRFFJGDFG-UHFFFAOYSA-N 0.000 claims 2
- NYCXYKOXLNBYID-UHFFFAOYSA-N 5,7-Dihydroxychromone Natural products O1C=CC(=O)C=2C1=CC(O)=CC=2O NYCXYKOXLNBYID-UHFFFAOYSA-N 0.000 claims 1
- 108010028091 Albulin Proteins 0.000 claims 1
- 229940043370 chrysin Drugs 0.000 claims 1
- 235000015838 chrysin Nutrition 0.000 claims 1
- 239000012931 lyophilized formulation Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 30
- 230000027455 binding Effects 0.000 description 25
- 238000009739 binding Methods 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 23
- 108090000765 processed proteins & peptides Proteins 0.000 description 22
- 230000035772 mutation Effects 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 238000009472 formulation Methods 0.000 description 14
- 229920001184 polypeptide Polymers 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 14
- 235000002639 sodium chloride Nutrition 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 12
- 238000004422 calculation algorithm Methods 0.000 description 12
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 11
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 11
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 150000007523 nucleic acids Chemical group 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 108020004707 nucleic acids Proteins 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000001794 hormone therapy Methods 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 239000003053 toxin Substances 0.000 description 6
- 231100000765 toxin Toxicity 0.000 description 6
- 108700012359 toxins Proteins 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- -1 arbrin ) A chain Proteins 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 238000011580 nude mouse model Methods 0.000 description 5
- 238000011275 oncology therapy Methods 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 238000012879 PET imaging Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000001415 gene therapy Methods 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 229940127121 immunoconjugate Drugs 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000283707 Capra Species 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108700012941 GNRH1 Proteins 0.000 description 3
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000973510 Homo sapiens Melanoma-derived growth regulatory protein Proteins 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000002280 anti-androgenic effect Effects 0.000 description 3
- 239000000051 antiandrogen Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 206010070308 Refractory cancer Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 230000002494 anti-cea effect Effects 0.000 description 2
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 102000050405 human PSCA Human genes 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000010603 microCT Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 238000011474 orchiectomy Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 238000002818 protein evolution Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000012217 radiopharmaceutical Substances 0.000 description 2
- 229940121896 radiopharmaceutical Drugs 0.000 description 2
- 230000002799 radiopharmaceutical effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.O([C@@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 241001272178 Glires Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000746783 Homo sapiens Cytochrome b-c1 complex subunit 6, mitochondrial Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 229910009891 LiAc Inorganic materials 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 238000012338 Therapeutic targeting Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000013059 antihormonal agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 150000001508 asparagines Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000011347 external beam therapy Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010033706 glycylserine Proteins 0.000 description 1
- 239000002434 gonadorelin derivative Substances 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000048342 human MIA Human genes 0.000 description 1
- 102000048638 human UQCRH Human genes 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000002500 microbody Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108010010621 modeccin Proteins 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001915 proofreading effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011472 radical prostatectomy Methods 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 102200070760 rs1057519553 Human genes 0.000 description 1
- 102220295059 rs1555933649 Human genes 0.000 description 1
- 102200050839 rs386833792 Human genes 0.000 description 1
- 102220096713 rs876659643 Human genes 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- NGSFWBMYFKHRBD-UHFFFAOYSA-M sodium lactate Chemical class [Na+].CC(O)C([O-])=O NGSFWBMYFKHRBD-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
- A61K51/1096—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a radioactive nucleus for use in radiotherapeutic applications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57434—Specifically defined cancers of prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/626—Diabody or triabody
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
Description
該当なし
本発明は、NIH/NCIによって与えられた助成金番号CA092131の政府支援を受けて創出された。政府は、本発明において一定の権利を有する。
該当なし
本発明は、前立腺およびその他の癌において、高親和性で新規細胞表面マーカーを認識する改変抗体を記載する。これらの遺伝的に改変された抗体断片は、ターゲッティングおよび検出のためのインビボ使用に明確に適合している。
かの実施形態では、上記治療薬は、細胞傷害性薬剤である。例えば、上記薬剤は、リシン、リシンA鎖、ドキソルビシン、ダウノルビシン、タキソール、エチジウム(ethiduim)
ブロマイド、マイトマイシン、エトポシド、テノポシド(tenoposide)、ビンクリスチン、ビンブラスチン、コルヒチン、ジヒドロキシアントラシン(anthracin)ジオン、アクチノマイシンD、ジフテリア(diphteria)毒素、シュードモナス外毒素(PE)A、PE40、アブリン、アルブリン(arbrin)A鎖、モデクシン(modeccin)A鎖、α−サルシン、ゲロニン、ミトゲリン(mitogellin)、レトストリクトシ(retstrictocin)、
フェノマイシン(phenomycin)、エノマイシン(enomycin)、クリシン(curicin)、クロチン(crotin)、カリケアマイシン(calicheamicin)、サパオナリアオフィシナリス(sapaonaria officinalis)インヒビター、マイタンシノイド類またはグルココルチコイドリシンであり得る。その他の実施形態では、治療薬は、放射性同位元素である。放射性同位元素は、例えば、212Bi、131I、111In、90Yおよび186Reから
なる群から選択され得る。その他の実施形態では、構築物は、プロドラッグをその活性型に変換できる抗癌薬プロドラッグ活性化酵素と連結している。
ヒトPSCAである。
94Tcなどをはじめ、多数の放射性核種を画像化標識として使用してよい。当業者ならば、本発明における使用に特によく適している、その他の放射性核種を承知しているであろう。
造影剤および治療薬としての完全抗体の開発は、インビボで腫瘍標的に放射性核種を効果的にデリバリーするその能力にもかかわらず、長いクリアランス動態によって妨げられてきた。ここで、本発明者らはまた、ヌードマウスモデルにおける循環からの迅速なクリアランスと併せて、迅速で、高レベルの腫瘍取り込みを示す遺伝的に改変された抗体断片によって、インビボで腫瘍を容易に検出することが可能になることを報告する。
その他の実施形態では、抗PSCA抗体は、親和性成熟抗体であり得、上記親和性成熟抗体は、PSCAに対して、親抗体がなすよりも高い親和性を含む。特定の実施形態では、親の抗PSCA抗体は、1G8(ATCC番号HB−12612)、2A2(ATCC番号HB−1203)、2H9(ATCC番号HB−12614)、3C5(ATCC番号HB−12616)、3E6(ATCC番号HB12618)、3G3(ATCC番号HB−12615)、4A10(ATCC番号HB−12617)および2B3からなる群から選択され得る。その他の実施形態では、CDRは、配列番号10、11、12および13中に見られるものから選択され得る。
それに連結されている重鎖(VH)可変ドメイン(VH−VL)(第1のポリペプチド鎖上のその2つのドメイン間で対形成するには短すぎるペプチドリンカーによって接続されている)を含む第1のポリペプチド鎖と、第2のポリペプチド鎖上の重鎖可変ドメインVHおよび、それに連結されている軽鎖可変ドメイン(VL)(VL−VH)(第2のポリペプチド鎖上のその2つのドメイン間で対形成するには短すぎるペプチドリンカーによって接続されている)を含む第2のポリペプチド鎖とを含む。その短い結合が、第1および第2のポリペプチド鎖の相補的なドメイン間の鎖の対形成を推し進め、2つの機能的抗原結合部位を有する二量体分子の組み立てを促進する。
MKAVLLALLMAGLALQPGTALLCYSCKAQVSNEDCLQV
ENCTQLGEQCWTARIRAVGLLTVISKGCSLNCVDDS
QDYYVGKKNITCCDTDLCNASGAHALQPAAAILALLPAL
GLLLWGPGQL
(配列番号1)
以下に記載されるデフォルトパラメータを用いてBLASTまたはBLAST2.0配列比較アルゴリズムを使用して、または手作業でのアラインメントおよび目視検査によって測定されるような、比較ウィンドウもしくは指定された領域にわたる最大一致を求めて比較およびアラインされた場合に、参照される配列もしくは部分にわたって、同一であるか、または特定のパーセンテージの同一であるアミノ酸残基もしくはヌクレオチド(すなわち、約80%の同一性、好ましくは、少なくとも65%、70%、75%、80%、85%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%以上の同一性)を有する2種以上の配列または部分配列を指す(例えば、NCBIウェブサイトhttp://www.ncbi.nlm.nih.gov/BLAST/などをを参照のこと)。この定義はまた、欠失および/または付加を有する配列ならびに置換を有するものを含む。配列同一性は、2種の参照されるドメイン間で少なくとも85%、90%、95%、97%であることが好ましい。いくつかの実施形態では、配列の相違は、参照される配列またはドメインについて1、2、3または4または5〜12個のアミノ酸だけである。以下に記載されるように、好ましいアルゴリズムは、ギャップなどを説明することができる。同一性は、少なくとも約15個のアミノ酸またはヌクレオチドの長さである領域にわたって存在することが好ましく、15〜50個のアミノ酸またはヌクレオチドの長さである領域にわたって存在することがより好ましい。その他の実施形態では、同一性は、少なくとも約50、100、150、200個以上のアミノ酸である領域にわたって存在し得る。
によって推奨される一文字記号のいずれかによって呼ばれ得る。同様に、ヌクレオチドも、その一般に受け入れられた一文字コードによって呼ばれ得る。
グリシン(G);2)アスパラギン酸(D)、グルタミン酸(E);3)アスパラギン(N)、グルタミン(Q);4)アルギニン(R)、リシン(K);5)イソロイシン(I)、ロイシン(L)、メチオニン(M)、バリン(V);6)フェニルアラニン(F)、
チロシン(Y)、トリプトファン(W);7)セリン(S)、トレオニン(T);および8)システイン(C)、メチオニン(M)(例えば、Creighton, Proteins (1984)を参照のこと)。
例えば、組換え、モノクローナルまたはポリクローナル抗体、当技術分野で公知の多数の技術を使用してよい(特に、ミニボディーおよびダイアボディー設計に関して、その全文が、各々、参照により組み込まれる、米国特許出願公開第20070196274号および同20050163782号明細書を参照のこと)(例えば、Kohler & Milstein, Nature 256: 495-497 (1975); Kozbor et al., Immunology Today 4: 72 (1983); Cole et al., pp. 77-96 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985); Coligan, Current Protocols in Immunology (1991); Harlow & Lane, Antibodies
, A Laboratory Manual (1988);およびGoding, Monoclonal Antibodies: Principles and Practice (第2版、1986)を参照のこと)。注目する抗体の重鎖および軽鎖をコードする遺伝子を、細胞からクローニングしてもよく、例えば、モノクローナル抗体をコードする遺伝子を、ハイブリドーマからクローニングし、組換えモノクローナル抗体を製造するために使用してもよい。モノクローナル抗体の重鎖および軽鎖をコードする遺伝子ライブラリーはまた、ハイブリドーマまたは形質細胞から作製してもよい。重鎖および軽鎖遺伝子産物の無作為組合せによって、異なる抗原特異性を有する抗体の大きなプールが生じる(例えば、Kuby, Immunology (第3版、1997)を参照のこと)。単鎖抗体または組換え抗体の製造のための技術(米国特許第4,946,778号、同4,816,567号明細書)を適応させて、本発明のポリペプチドに対する抗体を製造してもよい。また、ヒト化またはヒト抗体を発現するために、トランスジェニックマウスまたはその他の哺乳類などのその他の生物を使用してもよい(例えば、米国特許第5,545,807号;同5,545,806号;同5,569,825号;同5,625,126号;同5,633,425号;同5,661,016号明細書、Marks et al., Bio/Technology 10: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368: 812-13 (1994); Fishwild et al., Nature Biotechnology 14: 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996);およびLonberg & Huszar, Intern. Rev. Immunol. 13: 65-93 (1995)を参照のこと)。あるいは、ファージディスプレイ技術を使用して、選択された抗原と特異的に結合する抗体およびヘテロマーFab断片を同定してもよい(例えば、McCafferty et al., Nature 348: 552-554 (1990); Marks et al., Biotechnology 10: 779-783 (1992)を参照のこと)。抗体はまた、二重特異性にすることができる、すなわち、2種の異なる抗原を認識できる(例えば、国際公開第93/08829号パンフレット、Traunecker et al., EMBO J. 10: 3655-3659 (1991);およびSuresh et al., Methods in Enzymology 121: 210 (1986)を参照のこと)。抗体はまた、ヘテロコンジュゲート、例えば、2種の共有結合によって結合している抗体または免疫毒素であってもよい(例えば、米国特許第4,676,980号明細書、国際公開第91/00360号;同第92/200373号パンフレット;および欧州特許第03089号明細書を参照のこと)。
、酵素、リンホカイン、オンコスタチンまたは毒素を挙げることができる。適した毒素として、ドキソルビシン、ダウノルビシン、タキソール、エチジウム(ethiduim)ブロマイド、マイトマイシン、エトポシド、テノポシド、ビンクリスチン、ビンブラスチン、コルヒチン、ジヒドロキシアントラシンジオン、アクチノマイシンD、ジフテリア(diphteria)毒素、シュードモナス外毒素(PE)A、PE40、リシン、アブリン、グルココルチコイドおよび放射性同位元素が挙げられる。
Antibodies For Immunotargeting Of Drugs In Cancer Therapy」、pp. 243-56 (Alan R.
Liss, Inc. 1985);「Controlled Drug Delivery」(第2版)、Robinsonら(編)中の、Hellstromら、「Antibodies For Drug Delivery」、pp. 623-53 (Marcel Dekker, Inc. 1987);「Monoclonal Antibodies ’84: Biological And Clinical Applications」、Pincheraら(編)中の、Thorpe、「Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review」、pp. 475-506 (1985);およびThorpe et al., 「The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates」, Immunol. Rev., 62: 119-58 (1982)を参照のこと)。
, Gennaro, Editor (2003)およびPickar, Dosage Calculations (1999)を参照のこと)。
予後および処置において特に適用される。特定の実施形態では、方法は、ホルモン不応性癌または治療抵抗性癌に適用される。特定の実施形態では、方法は転移性癌に適用される。
構築物は、静脈内投与などの公知の方法を踏まえて、例えば、ボーラスとして、または一定時間にわたる持続注入によって、筋肉内、腹腔内、脳脊髄内(intracerobrospinal)
、皮下、関節内、滑液包内、くも膜下腔内、経口、局所または吸入経路によって被験体に投与される。静脈内または皮下投与が好ましい。投与は、局所であっても、全身であってもよい。
、放射線療法(外部ビームまたは近接照射療法)、ホルモン治療(例えば、精巣摘出術、
テストステロン産生を抑制するためのLHRH−類似体治療、抗アンドロゲン療法)または化学療法と一緒に実施してよい。前立腺全摘除術は、前立腺全体およびいくらかの周囲組織の除去を含む。この治療は、癌が組織を越えて広がっていないと考えられる場合によく使用される。放射線療法は、まだ前立腺に限定されているか、隣接する組織に広がっている前立腺癌を治療するためによく使用される。疾患がより進行性である場合には、腫瘍の大きさを減少させるために放射線を使用する場合もある。ホルモン療法は、前立腺癌が前立腺を越えて広がった、または再発した患者に使用されることが多い。ホルモン療法の目的は、男性ホルモン、アンドロゲンのレベルを低下させ、それによって、前立腺癌を収縮させるか、より低速で増殖させる。黄体形成ホルモン放出ホルモン(LHRH)アゴニストは、テストステロンの産生を減少させる。これらの薬剤は、毎月、またはそれより長い間隔で注射してもよい。2種のこのような類似体として、ロイプロリドおよびゴセレリンがある。抗アンドロゲン(例えば、フルタミド、ビカルタミドおよびニルタミド)も使用してよい。全アンドロゲン遮断とは、精巣摘出術またはLHRH類似体と組み合わせた抗アンドロゲンの使用を意味し、s組合せが呼ばれる。化学療法は、前立腺癌が前立腺の外側に広がっており、ホルモン療法が失敗している患者にとっての選択肢である。癌細胞のすべてを破壊することは期待されないが、腫瘍増殖を低速にし、疼痛を低減し得る。ホルモン療法を用いる処置後に回復または継続して増殖し、広がった前立腺癌を治療するのに使用されるいくつかの化学療法薬として、ドキソルビシン(アドリアマイシン)、エストラムスチン、エトポシド、ミトキサントロン、ビンブラスチンおよびパクリタキセルが挙げられる。癌細胞が化学療法に対して耐性になる可能性を低減するために、2種以上の薬剤を一緒に投与することも多い。小さい細胞癌腫は、ホルモン療法よりも化学療法に応じる可能性がより高い、稀な種類の前立腺癌である。
特定の実施形態では、本発明は、本発明の抗体の投与によって、インビボで癌細胞または腫瘍を画像化する方法を提供する。一実施形態では、本発明は、インビボで癌細胞を画像化する方法を提供し、この方法は、哺乳類に標識された抗PSCA抗体を投与することおよびインビボで抗体を画像化することを含む。本発明の方法を使用して、哺乳類、例えば、限定するものではないが、マウス、ラット、ハムスター、ウサギ、ブタ、ヒトなどにおいて癌細胞を画像化することができる。
)、コンピュータ断層撮影(CAT)スキャン、冷却電荷結合素子(CCD)カメラ光学画像化(Honigman, et al., 2001 Mol. Ther. 4: 239-249)、生物発光光学画像化(P R Contag, et al., 1998 Nat. Med. 4: 245-247)、ポジトロン放出断層撮影(PET)(M E Phelps, 1991 Neurochemical Research 16: 929-994; J G Tjuvajev, et al., 1998 Cancer Res 58: 4333-4341)、単一光子放射コンピュータ断層撮影法(J G. Tjuvajev, et al., 1996 Cancer Res. 45: 4087-4095)、マイクロPET(McVeigh, 2006, Circ. Res. 98: 879-86に概説される)などが挙げられる。
本実施例は、突然変異体scFv酵母ディスプレイライブラリーの構築およびPSCA
結合親和性が改善されたScFv突然変異体の選択を記載する。
この実施例は、突然変異体2B3 scFvのミニボディーへの再編成を記載する。
この実施例では、抗PSCAミニボディーの発現、選択および精製を記載する。
. J Immunol Methods. 2001; 253: 195)、10μgの直線化(SalIで切断した)ベクターDNAを用い、エレクトロポレーションによってトランスフェクトし、グルタミン欠乏培地で選択した。クローンをELISAによって発現についてスクリーニングし、それによって、所望のタンパク質をヤギ抗ヒトIgG(Fc特異的)によって獲得し、アルカリホスファターゼ(AP)コンジュゲートヤギ抗ヒトIgG(Fc特異的)によって検出した(両方とも、Jackson ImmunoResearch Labs、West Grove、PA製)。最大に産生するクローンを増殖させ、最終培養に移した。
[実施例4]
Technologies、Indianapolis、INによって提供された陽電子放出同位元素l24I(0
.02M NaOH中ヨウ化ナトリウム;放射性核種純度>99%)を用いて放射性ヨウ素化した(Kenanova, Olafsen et al., Cancer Res. 65: 622, 2005)。免疫反応は、放射性ヨウ素化したミニボディーを、過剰量のSKW−PSCA+細胞とともに室温で1時間インキュベートし、細胞を遠心分離し、対照と比較して上清中に存在する放射能をカウントすることによってアッセイした。
この実施例は、抗PSCAミニボディーのマイクロPET画像化および生体内分布研究を記載する。
識ミニボディーを、右肩にLAPC−9AD腫瘍を保持するヌードマウスに注射した。21時間および/または25時間に全身マイクロ(mico)PETおよびCTスキャンを実施し、その後、動物を屠殺し、γカウンターを使用して種々の組織における活性を定量化した。マイクロPET画像化を定量化するために、腫瘍において4種の3次元ROIを描き、腫瘍周辺の軟組織中の4種のその他のROIが図6に提示されている。ROI位置および大きさは、CT画像情報を基にした。体内分布および画像化定量化の両方とも、バックグラウンドに対する腫瘍シグナルの比として表される。A11ミニボディーは、3種の親和性変異体を比較した実験において最良の体内分布および画像化データを示した(図7A)。したがって、3種の親和性変異体ミニボディーの、親和性順位(図5)およびインビボ腫瘍ターゲッティング/画像化順位(図7A)は異なっており、このことは、本発明者らのモデルでは、インビボ腫瘍ターゲッティング/画像化有効性は、単に、トレーサーの、その標的に対する固有の親和性に依存するものではないということを示唆する。PSCAに対して最良の親和性を有するA2は、最良のインビボ腫瘍ターゲッティング/画像化結果を示さなかった。この不一致についての1つの可能性ある説明は、A2は、VL CDR2中にアスパラギンのチロシンへの置換を有し、この新しいチロシンのヨウ素化が、PSCAとの結合に影響を及ぼし得るということである。第2の実験では、A11ミニボディーを、そのインビボ腫瘍ターゲッティング/画像化効率について親のミニボディーと比較した。A11は、腫瘍ターゲッティングにおける20%の増大(n=3)およびマイクロPET腫瘍画像化における141%の増大(n=2)を示した(図7B)。
この実施例は、抗PSCAミニボディーを使用した種々の膵臓癌腫瘍の画像化を記載する。
1)Sundaresan, G., Yazaki, P. J., Shively, J. E., Finn, R. D., Larson, S. M.,
Raubitschek, A. A., Williams, L. E., Chatziioannou, A. F., Gambhir, S. S., and
Wu, A. M. (2003) Iodine-1 24 labeled engineered anti-CEA minibodies and diabodie
s allow highcontrast, antigen-specific small-animal PET imaging of xenografts in
athymic mice. J, Nucl. Med., 44: 1962-1969。
ly, J. E., Raubitschek, A. A., Morrison, S. L., Wu, A. M. and Reiter, R. E. (200
7) Targeting, imaging, and therapy using a humanized anti-prostate stem cell ant
igen (PSCA) antibody. J. lmmunotherapy 30: 396-405。
tate cancer (abstract). Cancer Biotherapy & Radiopharmaceuticals 21 : 391, 2006。
Claims (19)
- 前立腺幹細胞抗原(PSCA;配列番号1)に特異的に結合する抗原結合タンパク質であって、
a)配列番号5のVLおよびVHドメイン、
b)配列番号6のVLおよびVHドメイン、
c)配列番号7のVLおよびVHドメイン、
d)配列番号11のVLおよびVHドメイン、
e)配列番号12のVLおよびVHドメイン、または
f)配列番号13のVLおよびVHドメイン
を含むタンパク質。 - ミニボディー、ダイアボディー、scFv、またはscFv−Fcである、請求項1記載の抗原結合タンパク質。
- a)治療薬とコンジュゲートしているか、または
b)検出可能マーカーで標識されている、
請求項1または2記載の抗原結合タンパク質。 - 治療薬が細胞傷害性薬、放射性同位元素またはプロドラッグである、請求項3記載の抗原結合タンパク質。
- 細胞傷害性薬剤が、リシン、リシンA鎖、ドキソルビシン、ダウノルビシン、タキソール、エチジウムブロマイド、マイトマイシン、エトポシド、テノポシド、ビンクリスチン、ビンブラスチン、コルヒチン、ジヒドロキシアントラシンジオン、アクチノマイシンD、ジフテリア毒素、シュードモナス外毒素(PE)A、PE40、アブリン、アルブリンA鎖、モデクシンA鎖、α−サルシン、ゲロニン、ミトゲリン、レトストリクトシン、フェノマイシン、エノマイシン、クリシン、クロチン、カリケアマイシン、サパオナリアオフィシナリスインヒビター、マイタンシノイド類およびグルココルチコイドリシンからなる群から選択される、請求項4記載の抗原結合タンパク質。
- 放射性同位元素が、212Bi、131I、124I、111In、90Yおよび186Reからなる群から選択される、請求項4記載の抗原結合タンパク質。
- 検出可能マーカーが、放射性同位元素、蛍光化合物、生物発光化合物、金属キレート剤、酵素、および124Iからなる群から選択される、請求項3記載の抗原結合タンパク質。
- 請求項1または2記載の抗原結合タンパク質をコードするポリヌクレオチド。
- インビボで非ヒト哺乳動物における癌細胞を画像化する方法であって、請求項3記載の抗原結合タンパク質を対象に投与し、該抗原結合タンパク質を検出し、それにより、インビボで癌細胞を画像化することを含み、該抗原結合タンパク質が検出可能マーカーで標識されている、方法。
- 抗原結合タンパク質が磁気共鳴画像法(MRI)、核磁気共鳴(NMR)、コンピュータ断層撮影(CAT)スキャン、冷却電荷結合素子(CCD)カメラ光学画像化、生物発光光学画像化、ポジトロン放出断層撮影(PET)、単一光子放射コンピュータ断層撮影法、またはマイクロPETによって検出される、請求項9記載の方法。
- 前立腺幹細胞抗原(PSCA)タンパク質を発現する前立腺癌細胞の増殖を阻害する方法において使用するための請求項3記載の抗原結合タンパク質であって、該方法が、前記癌細胞を、前記癌細胞の増殖を阻害するのに有効な量の前記抗原結合タンパク質と接触させることを含む方法であり、前記抗原結合タンパク質が治療薬とコンジュゲートしている、抗原結合タンパク質。
- (a)該方法が前立腺癌細胞を死滅させるための方法であり、
(b)該抗原結合タンパク質が、アミノ酸位置22のロイシンで始まり、アミノ酸位置99のアラニンで終了する配列番号2に示されるPSCAタンパク質を認識および結合し、
(c)該方法が、該細胞に化学療法薬を投与することをさらに含み、または
(d)該方法が、該細胞に放射線療法を施すことをさらに含む、
請求項11記載の使用のための抗原結合タンパク質。 - 該方法が前立腺、膀胱または膵臓癌に罹患している患者を処置するための方法である、請求項11または12記載の使用のための抗原結合タンパク質。
- 該方法がホルモンアブレーション療法またはホルモンアンタゴニスト療法を患者に施すことを含む、請求項13記載の使用のための抗原結合タンパク質。
- (a)該抗原結合タンパク質を患者に静脈内、腹腔内、筋内、腫瘍内または皮内投与するか、または
(b)該抗原結合タンパク質を直接、前立腺癌、膀胱癌、膵臓癌、またはその転移中に投与する
ことを含む、請求項14記載の使用のための抗原結合タンパク質。 - 癌細胞を検出する方法において使用するための、請求項3記載の抗原結合タンパク質。
- 対象における前立腺、膀胱または膵臓癌の処置または検出において使用するための、請求項3記載の抗原結合タンパク質。
- 請求項3記載の抗原結合タンパク質と、医薬上許容される賦形剤、担体または安定剤とを含み、治療薬とコンジュゲートしている、医薬組成物。
- 凍結乾燥製剤または水溶液である、請求項18に記載の医薬組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US96993907P | 2007-09-04 | 2007-09-04 | |
US60/969,939 | 2007-09-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010524150A Division JP6126773B2 (ja) | 2007-09-04 | 2008-09-04 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017062817A Division JP2017158554A (ja) | 2007-09-04 | 2017-03-28 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015015960A JP2015015960A (ja) | 2015-01-29 |
JP6120819B2 true JP6120819B2 (ja) | 2017-04-26 |
Family
ID=40429695
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010524150A Active JP6126773B2 (ja) | 2007-09-04 | 2008-09-04 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
JP2014186846A Active JP6120819B2 (ja) | 2007-09-04 | 2014-09-12 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
JP2017062817A Pending JP2017158554A (ja) | 2007-09-04 | 2017-03-28 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010524150A Active JP6126773B2 (ja) | 2007-09-04 | 2008-09-04 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017062817A Pending JP2017158554A (ja) | 2007-09-04 | 2017-03-28 | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Country Status (5)
Country | Link |
---|---|
US (2) | US8940298B2 (ja) |
EP (1) | EP2197491A4 (ja) |
JP (3) | JP6126773B2 (ja) |
CA (1) | CA2698343C (ja) |
WO (1) | WO2009032949A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017158554A (ja) * | 2007-09-04 | 2017-09-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
US6541212B2 (en) | 1997-03-10 | 2003-04-01 | The Regents Of The University Of California | Methods for detecting prostate stem cell antigen protein |
US9701754B1 (en) | 2002-10-23 | 2017-07-11 | City Of Hope | Covalent disulfide-linked diabodies and uses thereof |
EP1996716B1 (en) | 2006-03-20 | 2011-05-11 | The Regents of the University of California | Engineered anti-prostate stem cell antigen (psca) antibodies for cancer targeting |
WO2010096486A1 (en) | 2009-02-17 | 2010-08-26 | Cornell Research Foundation, Inc. | Methods and kits for diagnosis of cancer and prediction of therapeutic value |
CA2782333C (en) | 2009-12-02 | 2019-06-04 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
EP2621953B1 (en) | 2010-09-30 | 2017-04-05 | Ablynx N.V. | Biological materials related to c-met |
US11644471B2 (en) * | 2010-09-30 | 2023-05-09 | Ablynx N.V. | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
CN103561771B (zh) | 2011-03-17 | 2019-01-04 | 伯明翰大学 | 重新定向的免疫治疗 |
AU2012271974B2 (en) | 2011-06-23 | 2017-01-12 | Ablynx Nv | Serum albumin binding proteins |
US20150344568A1 (en) * | 2011-06-23 | 2015-12-03 | Ablynx N.V. | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
SG10201805064SA (en) | 2011-06-23 | 2018-07-30 | Ablynx Nv | Techniques for predicting, detecting and reducing aspecific protein interference in assays involving immunoglobulin single variable domains |
DE102011118022B4 (de) * | 2011-06-30 | 2018-01-18 | Gemoab Monoclonals Gmbh | Antikörper gegen das Prostata-spezifische Stammzellenantigen und dessen Verwendung |
US10035009B2 (en) | 2013-04-15 | 2018-07-31 | The Board Of Trustees Of The Leland Stanford Junior University | Systems and methods for treating pancreatic cancer |
NZ739721A (en) | 2015-08-07 | 2019-09-27 | Imaginab Inc | Antigen binding constructs to target molecules |
ES2809550T3 (es) | 2015-10-06 | 2021-03-04 | Hope City | Receptores de antígenos quiméricos dirigidos contra PSCA |
WO2018147960A1 (en) | 2017-02-08 | 2018-08-16 | Imaginab, Inc. | Extension sequences for diabodies |
CN107602704A (zh) * | 2017-09-11 | 2018-01-19 | 贵州医科大学 | 一种抗***癌干细胞抗原单链抗体融合蛋白的制备方法 |
CN113423822A (zh) * | 2018-12-13 | 2021-09-21 | 贝里坤制药股份有限公司 | Psca car-t细胞 |
EP3897851A2 (en) | 2018-12-17 | 2021-10-27 | Revitope Limited | Twin immune cell engager |
JP2022547552A (ja) * | 2019-09-11 | 2022-11-14 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 前立腺幹細胞抗原(psca)キメラ抗原受容体(car)を含む組成物および方法 |
Family Cites Families (252)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US121022A (en) | 1871-11-14 | Improvement in harness-fviountings | ||
US943525A (en) | 1908-01-04 | 1909-12-14 | William Henry Drake | Folding crate. |
US4444878A (en) | 1981-12-21 | 1984-04-24 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
US5292668A (en) | 1981-12-21 | 1994-03-08 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
US5869620A (en) | 1986-09-02 | 1999-02-09 | Enzon, Inc. | Multivalent antigen-binding proteins |
US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
FR2604092B1 (fr) | 1986-09-19 | 1990-04-13 | Immunotech Sa | Immunoreactifs destines a cibler les cellules animales pour leur visualisation ou leur destruction in vivo |
EP0382736B1 (en) | 1987-07-27 | 1994-11-02 | Commonwealth Scientific And Industrial Research Organisation | Receptor membranes |
US5766960A (en) | 1987-07-27 | 1998-06-16 | Australian Membrane And Biotechnology Research Institute | Receptor membranes |
US4943525A (en) | 1987-11-02 | 1990-07-24 | Bioventures, Inc. | Simultaneous immunoassay for the determination of antigens and antibodies |
US4892824A (en) | 1988-03-15 | 1990-01-09 | Synbiotics Corporation | Fast track method for producing monoclonal bi-specific immunoglobulins |
US6010902A (en) | 1988-04-04 | 2000-01-04 | Bristol-Meyers Squibb Company | Antibody heteroconjugates and bispecific antibodies for use in regulation of lymphocyte activity |
US20030068322A1 (en) | 1988-04-18 | 2003-04-10 | Immunomedics, Inc. | Methods of antibody-directed enzyme-prodrug therapy |
US5851527A (en) | 1988-04-18 | 1998-12-22 | Immunomedics, Inc. | Method for antibody targeting of therapeutic agents |
KR0184860B1 (ko) | 1988-11-11 | 1999-04-01 | 메디칼 리써어치 카운실 | 단일영역 리간드와 이를 포함하는 수용체 및 이들의 제조방법과 이용(법) |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US6020145A (en) | 1989-06-30 | 2000-02-01 | Bristol-Myers Squibb Company | Methods for determining the presence of carcinoma using the antigen binding region of monoclonal antibody BR96 |
US5980896A (en) | 1989-06-30 | 1999-11-09 | Bristol-Myers Squibb Company | Antibodies reactive with human carcinomas |
IL94872A (en) | 1989-06-30 | 1995-03-30 | Oncogen | Monoclonal or chimeric antibodies that react with human carcinoma, recombinant proteins that contain their anti-binding site, pharmaceutical preparations and kits that contain the |
US5332567A (en) | 1989-08-24 | 1994-07-26 | Immunomedics | Detection and treatment of infections with immunoconjugates |
US5582996A (en) | 1990-12-04 | 1996-12-10 | The Wistar Institute Of Anatomy & Biology | Bifunctional antibodies and method of preparing same |
CA2065658A1 (en) | 1991-04-19 | 1992-10-20 | Tse-Wen Chang | Conjugates of liposomes or microbeads and antibodies specific for t lymphocytes and their use in vivo immune modulators |
US6129916A (en) | 1991-04-19 | 2000-10-10 | Tanox, Inc. | Method of Increasing activation on proliferation of T cells using antibody-microbead conjugates |
US6106835A (en) | 1991-04-19 | 2000-08-22 | Tanox, Inc. | Modified binding molecules specific for T or B lymphocytes and their use as in vivo immune modulators |
US5872222A (en) | 1991-04-19 | 1999-02-16 | Tanox Biosystems, Inc. | Conjugates of polymers and antibodies specific for T lymphocytes, and their use as adjuvants |
US6197298B1 (en) | 1991-04-19 | 2001-03-06 | Tanox, Inc. | Modified binding molecules specific for T lymphocytes and their use as in vivo immune modulators in animals |
DE4118120A1 (de) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung |
AU661854B2 (en) | 1991-06-27 | 1995-08-10 | Bristol-Myers Squibb Company | CTL4A receptor, fusion proteins containing it and uses thereof |
US6090914A (en) | 1991-06-27 | 2000-07-18 | Bristol-Myers Squibb Company | CTLA4/CD28Ig hybrid fusion proteins and uses thereof |
US6887471B1 (en) | 1991-06-27 | 2005-05-03 | Bristol-Myers Squibb Company | Method to inhibit T cell interactions with soluble B7 |
US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
US5770197A (en) | 1991-06-27 | 1998-06-23 | Bristol-Myers Squibb Company | Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules |
US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
DE4134982A1 (de) | 1991-10-23 | 1993-04-29 | Kernforschungsz Karlsruhe | Verwendung von antikoerper enthaltenden praeparationen zur immunsuppression |
US5932448A (en) | 1991-11-29 | 1999-08-03 | Protein Design Labs., Inc. | Bispecific antibody heterodimers |
DE4140142A1 (de) | 1991-12-05 | 1993-06-09 | Boehringer Mannheim Gmbh, 6800 Mannheim, De | Multivalentes dextranreagenz zum einsatz in praezipitationstests |
CA2125396A1 (en) | 1991-12-10 | 1993-06-24 | Wayne A. Marasco | Reactive neutralizing human anti-gp 120 recombinant antibody, dna coding the same and use thereof |
FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
AU675929B2 (en) | 1992-02-06 | 1997-02-27 | Curis, Inc. | Biosynthetic binding protein for cancer marker |
US5877289A (en) | 1992-03-05 | 1999-03-02 | The Scripps Research Institute | Tissue factor compositions and ligands for the specific coagulation of vasculature |
US6004555A (en) | 1992-03-05 | 1999-12-21 | Board Of Regents, The University Of Texas System | Methods for the specific coagulation of vasculature |
US6749853B1 (en) | 1992-03-05 | 2004-06-15 | Board Of Regents, The University Of Texas System | Combined methods and compositions for coagulation and tumor treatment |
US6093399A (en) | 1992-03-05 | 2000-07-25 | Board Of Regents, The University Of Texas System | Methods and compositions for the specific coagulation of vasculature |
EP0627940B1 (en) | 1992-03-05 | 2003-05-07 | Board of Regents, The University of Texas System | Use of immunoconjugates for the diagnosis and/or therapy of vascularized tumors |
US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
US5776427A (en) | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
US6096289A (en) | 1992-05-06 | 2000-08-01 | Immunomedics, Inc. | Intraoperative, intravascular, and endoscopic tumor and lesion detection, biopsy and therapy |
US5844094A (en) | 1992-09-25 | 1998-12-01 | Commonwealth Scientific And Industrial Research Organization | Target binding polypeptide |
AU5322494A (en) | 1992-10-02 | 1994-04-26 | Trustees Of Dartmouth College | Bispecific reagents for redirected targeting of low density lipoprotein |
US5837821A (en) | 1992-11-04 | 1998-11-17 | City Of Hope | Antibody construct |
EP1757694A3 (en) | 1992-11-05 | 2008-02-27 | Sloan Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
AU5670194A (en) | 1992-11-20 | 1994-06-22 | Enzon, Inc. | Linker for linked fusion polypeptides |
US5376249A (en) | 1992-11-25 | 1994-12-27 | Perseptive Biosystems, Inc. | Analysis utilizing isoelectric focusing |
GB9225453D0 (en) | 1992-12-04 | 1993-01-27 | Medical Res Council | Binding proteins |
JP3720353B2 (ja) | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | 多価および多重特異性の結合タンパク質、それらの製造および使用 |
ATE187494T1 (de) | 1992-12-11 | 1999-12-15 | Dow Chemical Co | Multivalente einkettige antikörper |
US5861156A (en) | 1993-01-08 | 1999-01-19 | Creative Biomolecules | Methods of delivering agents to target cells |
US5773253A (en) | 1993-01-22 | 1998-06-30 | Bristol-Myers Squibb Company | MYPPPY variants of CTL A4 and uses thereof |
US6482919B2 (en) | 1993-02-01 | 2002-11-19 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
CA2155335C (en) | 1993-02-04 | 2001-06-05 | HANS CHRISTIAN THõGERSEN | Improved method for the refolding of proteins |
US5705614A (en) | 1993-04-09 | 1998-01-06 | Chiron Corporation | Methods of producing antigen forks |
KR100398819B1 (ko) | 1993-09-02 | 2004-02-05 | 트러스티스 오브 다트마우스 칼리지 | gp39길항제를포함하는약제조성물 |
US5869049A (en) | 1993-09-02 | 1999-02-09 | Trustees Of Dartmouth College | Methods of inducing T cell unresponsiveness to bone marrow with gp39 antagonists |
NZ273207A (en) | 1993-09-02 | 1997-09-22 | Dartmouth College | Igg antibodies gp39 (cd40) |
AU680685B2 (en) | 1993-09-22 | 1997-08-07 | Medical Research Council | Retargeting antibodies |
GB9324807D0 (en) | 1993-12-03 | 1994-01-19 | Cancer Res Campaign Tech | Tumour antibody |
DE4421391C1 (de) | 1994-06-18 | 1995-11-30 | Gsf Forschungszentrum Umwelt | Verwendung von Antikörpern gegen T-Zellen zur verlängerten Immunsuppression |
US5559099A (en) | 1994-09-08 | 1996-09-24 | Genvec, Inc. | Penton base protein and methods of using same |
US5962311A (en) | 1994-09-08 | 1999-10-05 | Genvec, Inc. | Short-shafted adenoviral fiber and its use |
US5846782A (en) | 1995-11-28 | 1998-12-08 | Genvec, Inc. | Targeting adenovirus with use of constrained peptide motifs |
US5965541A (en) | 1995-11-28 | 1999-10-12 | Genvec, Inc. | Vectors and methods for gene transfer to cells |
US6465253B1 (en) | 1994-09-08 | 2002-10-15 | Genvec, Inc. | Vectors and methods for gene transfer to cells |
US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
US5688690A (en) | 1994-09-16 | 1997-11-18 | The Wistar Institute Of Anatomy And Biology | Human cytotoxic lymphocyte signal transduction surface protein (P38) and monoclonal antibodies thereto |
DE69635801T2 (de) | 1995-02-24 | 2006-11-02 | Sloan-Kettering Institute For Cancer Research | Prostataspezifisches membranes antigen und seine anwendungen |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
GB9504344D0 (en) | 1995-03-03 | 1995-04-19 | Unilever Plc | Antibody fragment production |
US5837281A (en) | 1995-03-17 | 1998-11-17 | Takeda Chemical Industries, Ltd. | Stabilized interface for iontophoresis |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
US5747035A (en) | 1995-04-14 | 1998-05-05 | Genentech, Inc. | Polypeptides with increased half-life for use in treating disorders involving the LFA-1 receptor |
AUPO591797A0 (en) | 1997-03-27 | 1997-04-24 | Commonwealth Scientific And Industrial Research Organisation | High avidity polyvalent and polyspecific reagents |
US5830478A (en) | 1995-06-07 | 1998-11-03 | Boston Biomedical Research Institute | Method for delivering functional domains of diphtheria toxin to a cellular target |
WO1997014719A1 (en) | 1995-10-16 | 1997-04-24 | Unilever N.V. | A bifunctional or bivalent antibody fragment analogue |
US5840854A (en) | 1995-10-19 | 1998-11-24 | Bristol-Myers Squibb Company | Monoclonal antibody BR110 and uses thereof |
US6150508A (en) | 1996-03-25 | 2000-11-21 | Northwest Biotherapeutics, Inc. | Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen |
US6962981B1 (en) | 1996-03-25 | 2005-11-08 | Medarex, Inc. | Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen |
IL126314A (en) | 1996-03-25 | 2003-07-31 | Northwest Biotherapeutics Inc | Monoclonal antibodies having an antigen binding region specific for the extracellular domain of prostate specific membrane antigen (psma) |
US7381407B1 (en) | 1996-03-25 | 2008-06-03 | Medarex, Inc. | Monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen |
US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
EP0901630B1 (en) | 1996-05-23 | 2003-08-20 | Inverness Medical Switzerland GmbH | Improvements in or relating to specific binding assays |
JP2000515735A (ja) | 1996-07-03 | 2000-11-28 | ジェネンテック インコーポレーテッド | 肝細胞成長因子レセプターアゴニスト |
GB9712818D0 (en) | 1996-07-08 | 1997-08-20 | Cambridge Antibody Tech | Labelling and selection of specific binding molecules |
US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
US6653104B2 (en) | 1996-10-17 | 2003-11-25 | Immunomedics, Inc. | Immunotoxins, comprising an internalizing antibody, directed against malignant and normal cells |
JP2001503253A (ja) | 1996-10-17 | 2001-03-13 | イムノメディクス,インコーポレイテッド | 非抗原性即素複合体およびインターナライジング受容体システムの融合タンパク |
WO1998029736A1 (en) | 1996-12-31 | 1998-07-09 | Genometrix Incorporated | Multiplexed molecular analysis apparatus and method |
US6960443B2 (en) | 1997-03-10 | 2005-11-01 | The Regents Of The University Of California | Methods of detecting prostate stem cell antigen in cancer |
US6541212B2 (en) | 1997-03-10 | 2003-04-01 | The Regents Of The University Of California | Methods for detecting prostate stem cell antigen protein |
US6261789B1 (en) * | 1997-03-10 | 2001-07-17 | The Regents Of The University Of California | Methods for detecting the presence of a PSCA protein using PSCA antibodies |
US6261791B1 (en) | 1997-03-10 | 2001-07-17 | The Regents Of The University Of California | Method for diagnosing cancer using specific PSCA antibodies |
US20080318254A9 (en) | 1997-03-10 | 2008-12-25 | The Regents Of The University Of California | PSCA antibodies and hybridomas producing them |
NZ337413A (en) | 1997-03-10 | 2003-02-28 | Univ California | Antibodies that bind to Prostate Stem Cell Antigen (PSCA) to treat prostate cancer. |
US6258939B1 (en) | 1997-03-10 | 2001-07-10 | The Regents Of The University Of California | PSCA antibodies and hybridomas producing them |
EP0977837A1 (en) | 1997-04-03 | 2000-02-09 | Universite Laval | Transgenic expression in genital tract and sexual accessory glands |
ATE302217T1 (de) | 1997-05-02 | 2005-09-15 | Us Gov Health & Human Serv | Immuntoxine, die ein onc protein enthalten, gegen bösartige zellen |
US6368596B1 (en) | 1997-07-08 | 2002-04-09 | Board Of Regents, The University Of Texas System | Compositions and methods for homoconjugates of antibodies which induce growth arrest or apoptosis of tumor cells |
US6994851B1 (en) | 1997-07-10 | 2006-02-07 | Mannkind Corporation | Method of inducing a CTL response |
US6977074B2 (en) | 1997-07-10 | 2005-12-20 | Mannkind Corporation | Method of inducing a CTL response |
JP3992923B2 (ja) | 1997-09-03 | 2007-10-17 | イムノメディクス, インコーポレイテッド | F−18陽電子放出トモグラフィー用のタン白及びペプチドのフッ素化方法 |
US6030792A (en) | 1997-11-13 | 2000-02-29 | Pfizer Inc | Assays for measurement of protein fragments in biological media |
US6709844B1 (en) | 2000-11-16 | 2004-03-23 | Mannkind Corporation | Avoidance of undesirable replication intermediates in plasmid propagation |
DE19911329A1 (de) | 1998-03-27 | 2000-09-21 | Benes Ivan Friedrich | Humantherapeutisch anwendbares Radioimmunkonjugat und Verfahren zu seiner Herstellung |
CZ121599A3 (cs) | 1998-04-09 | 1999-10-13 | Aventis Pharma Deutschland Gmbh | Jednořetězcová molekula vázající několik antigenů, způsob její přípravy a léčivo obsahující tuto molekulu |
AU3657899A (en) | 1998-04-20 | 1999-11-08 | James E. Bailey | Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity |
US6200765B1 (en) | 1998-05-04 | 2001-03-13 | Pacific Northwest Cancer Foundation | Non-invasive methods to detect prostate cancer |
US6071490A (en) | 1998-05-07 | 2000-06-06 | Immunomedics, Inc. | Position emission tomography using gallium-68 chelates |
AU742626B2 (en) | 1998-05-20 | 2002-01-10 | Immunomedics Inc. | Therapeutics using a bispecific anti-HLA class II invariant chain X anti-pathogen antibody |
ES2329851T3 (es) | 1998-06-01 | 2009-12-01 | Agensys, Inc. | Nuevos antigenos transmembranables expresados en canceres humano y utilizacion de los mismos. |
US20060052321A1 (en) | 2002-04-05 | 2006-03-09 | Raitano Arthur B | Nucleic acid and corresponding protein entitled 98P4B6 useful in treatment and detection of cancer |
US20040141975A1 (en) | 1998-06-01 | 2004-07-22 | Raitano Arthur B. | Nucleic acid and corresponding protein entitled 98P4B6 useful in treatment and detection of cancer |
CA2331789C (en) | 1998-07-13 | 2013-09-10 | Board Of Regents, The University Of Texas System | Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids |
AU5815699A (en) | 1998-09-08 | 2000-03-27 | Urocor, Inc. | Prostate specific promoter and regulation of gene expression |
US6361774B1 (en) | 1999-09-17 | 2002-03-26 | Immunomedics, Inc. | Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug |
CA2344655A1 (en) | 1998-09-29 | 2000-04-06 | The Uab Research Foundation | Immunomodulation by genetic modification of dendritic cells and b-cells |
US6642007B1 (en) | 1998-11-02 | 2003-11-04 | Pfizer Inc. | Assays for measurement of type II collagen fragments in urine |
WO2000034461A2 (en) | 1998-12-10 | 2000-06-15 | Board Of Regents, The University Of Texas System | Compositions and methods of modulating cholesterol metabolism |
EP1171468B1 (en) * | 1999-04-09 | 2008-07-02 | Universität Zürich | Method for the Stabilization of Chimeric Immunoglobulins or Immunoglobulin Fragments, and Stabilized Anti-EGP-2-scFv Fragment |
AU775583B2 (en) | 1999-04-13 | 2004-08-05 | Medarex, Inc. | Methods for the diagnosis and treatment of metastatic prostate tumors |
US6703020B1 (en) | 1999-04-28 | 2004-03-09 | Board Of Regents, The University Of Texas System | Antibody conjugate methods for selectively inhibiting VEGF |
WO2000064946A2 (en) | 1999-04-28 | 2000-11-02 | Board Of Regents, The University Of Texas System | Compositions and methods for cancer treatment by selectively inhibiting vegf |
GB9915653D0 (en) | 1999-07-06 | 1999-09-01 | Bruce Terry | Hose clamp |
WO2001009303A2 (en) | 1999-07-30 | 2001-02-08 | Vical Inc. | Flt-3 LIGAND-ENCODING POLYNUCLEOTIDE AS A POLYNUCLEOTIDE-BASED VACCINE ENHANCER |
KR20050004240A (ko) | 1999-08-31 | 2005-01-12 | 제넨테크, 인크. | 종양 치료용 조성물 및 방법 |
US6342587B1 (en) | 1999-10-22 | 2002-01-29 | Ludwig Institute For Cancer Research | A33 antigen specific immunoglobulin products and uses thereof |
US6346249B1 (en) | 1999-10-22 | 2002-02-12 | Ludwig Institute For Cancer Research | Methods for reducing the effects of cancers that express A33 antigen using A33 antigen specific immunoglobulin products |
IL149116A0 (en) * | 1999-10-29 | 2002-11-10 | Genentech Inc | Anti-prostate stem cell antigen (psca) antibody compositions and methods of use |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
EP1266009B1 (en) * | 2000-02-25 | 2008-12-31 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF |
JP2004500108A (ja) | 2000-03-24 | 2004-01-08 | マイクロメット アーゲー | Nkg2dレセプター複合体のエピトープへの結合部位を含む多機能ポリペプチド |
US6573096B1 (en) | 2000-04-01 | 2003-06-03 | The Research Foundation At State University Of New York | Compositions and methods for inhibition of cancer invasion and angiogenesis |
ES2528794T3 (es) | 2000-04-11 | 2015-02-12 | Genentech, Inc. | Anticuerpos multivalentes y usos de los mismos |
ATE474931T1 (de) | 2000-04-28 | 2010-08-15 | Mannkind Corp | Epitop-synchronisierung in antigen präsentierenden zellen |
US6861234B1 (en) | 2000-04-28 | 2005-03-01 | Mannkind Corporation | Method of epitope discovery |
US6375991B1 (en) | 2000-09-08 | 2002-04-23 | Albemarle Corporation | Production of concentrated biocidal solutions |
DE10045591A1 (de) | 2000-09-15 | 2002-04-04 | Klaus Pfizenmaier | Ortsspezifische, antikörpervermittelte Aktivierung proapoptotischer Zytokine - AMAIZe (Antibody-Mediated Apoptosis Inducing Zytokine) |
WO2003008537A2 (en) | 2001-04-06 | 2003-01-30 | Mannkind Corporation | Epitope sequences |
NZ592087A (en) | 2001-08-03 | 2012-11-30 | Roche Glycart Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
AU2002336446B2 (en) | 2001-09-06 | 2008-03-06 | Agensys, Inc. | Nucleic acid and corresponding protein entitled STEAP-1 useful in treatment and detection of cancer |
US7494646B2 (en) | 2001-09-06 | 2009-02-24 | Agensys, Inc. | Antibodies and molecules derived therefrom that bind to STEAP-1 proteins |
ES2326964T3 (es) | 2001-10-25 | 2009-10-22 | Genentech, Inc. | Composiciones de glicoproteina. |
EP2314712B1 (en) | 2001-11-07 | 2014-01-08 | Mannkind Corporation | Expression vectors encoding epitopes of antigens and methods for their design |
US20040018519A1 (en) | 2001-11-16 | 2004-01-29 | Wright ,Jr. George L | Methods and devices for quantitative detection of prostate specific membrane antigen and other prostatic markers |
JP4035845B2 (ja) | 2001-12-10 | 2008-01-23 | 株式会社グリーンペプタイド | 腫瘍抗原 |
US7452539B2 (en) | 2001-12-19 | 2008-11-18 | Genentech, Inc. | Stabilizing polypeptides which have been exposed to urea |
AU2003210802B2 (en) | 2002-02-05 | 2009-09-10 | Genentech Inc. | Protein purification |
CA2478925C (en) | 2002-04-26 | 2016-06-07 | Robert Lee Fahrner | Non-affinity purification of proteins |
JP2005530856A (ja) | 2002-06-21 | 2005-10-13 | ジョンズ ホプキンス ユニバーシティー スクール オブ メディシン | 膜関連腫瘍内皮マーカー |
US9809654B2 (en) | 2002-09-27 | 2017-11-07 | Vaccinex, Inc. | Targeted CD1d molecules |
US7820166B2 (en) | 2002-10-11 | 2010-10-26 | Micromet Ag | Potent T cell modulating molecules |
US9701754B1 (en) | 2002-10-23 | 2017-07-11 | City Of Hope | Covalent disulfide-linked diabodies and uses thereof |
PT1575517E (pt) * | 2002-12-24 | 2012-05-28 | Rinat Neuroscience Corp | Anticorpos anti-ngf e métodos de utilização dos mesmos |
ES2574993T3 (es) | 2003-01-22 | 2016-06-23 | Roche Glycart Ag | Construcciones de fusión y uso de las mismas para producir anticuerpos con mayor afinidad de unión al receptor de Fc y función efectora |
US7453436B2 (en) * | 2003-03-21 | 2008-11-18 | Ruiz David M | Hand-held on-screen control device |
WO2004088279A2 (en) | 2003-03-28 | 2004-10-14 | Iowa State University Research Foundation, Inc. | Allosteric probes and methods |
GB0308988D0 (en) | 2003-04-17 | 2003-05-28 | Univ Singapore | Molecule |
US7541442B2 (en) | 2003-05-30 | 2009-06-02 | Agensys, Inc. | Antibodies and related molecules that bind to PSCA proteins |
DK1629088T3 (da) | 2003-05-30 | 2012-05-07 | Agensys Inc | Varianter af prostatastamcelleantigen (psca) og undersekvenser deraf |
US7595379B2 (en) | 2003-05-30 | 2009-09-29 | Agensys, Inc. | Antibodies and related molecules that bind to PSCA proteins |
WO2004106380A2 (en) | 2003-05-31 | 2004-12-09 | Micromet Ag | Human-anti-human cd3 binding molecules |
US7700097B2 (en) | 2003-06-27 | 2010-04-20 | Biogen Idec Ma Inc. | Purification and preferential synthesis of binding molecules |
ES2786568T3 (es) | 2003-07-28 | 2020-10-13 | Genentech Inc | Reducción de la lixiviación de la proteína A durante la cromatografía de afinidad con proteína A |
GB0321805D0 (en) | 2003-09-18 | 2003-10-15 | Univ Wales Medicine | Human tumour growth patterns |
US7524813B2 (en) | 2003-10-10 | 2009-04-28 | Novo Nordisk Health Care Ag | Selectively conjugated peptides and methods of making the same |
KR101229731B1 (ko) | 2003-10-16 | 2013-03-07 | 암젠 리서치 (뮌헨) 게엠베하 | 다중특이적 탈면역화된 cd3-바인더 |
EP2641611A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
ITPD20030264A1 (it) | 2003-10-30 | 2005-04-30 | Xeptagen Spa | Metodo di diagnosi altamente specifico per neoplasie |
KR101520209B1 (ko) | 2003-11-06 | 2015-05-13 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
CA2553261C (en) | 2004-01-16 | 2014-03-18 | Stefan Barth | Immunokinases |
SI1716178T1 (sl) | 2004-02-16 | 2010-11-30 | Micromet Ag | Manj imunogene vezne molekule |
EP1718667B1 (en) | 2004-02-23 | 2013-01-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
CA2559870A1 (en) | 2004-04-07 | 2005-10-27 | Genetech,Inc. | Mass spectrometry of antibody conjugates |
EP1745157A4 (en) | 2004-04-12 | 2008-06-11 | Ohio Med College | METHODS AND COMPOSITIONS FOR ANALYZING ANALYTES |
ES2443996T3 (es) | 2004-04-22 | 2014-02-21 | Agensys, Inc. | Anticuerpos y moléculas derivadas de los mismos que se unen a proteínas STEAP-1 |
NZ551180A (en) | 2004-06-01 | 2009-10-30 | Genentech Inc | Antibody drug conjugates and methods |
WO2005118802A2 (en) | 2004-06-03 | 2005-12-15 | The Regents Of The University Of California | Targeting pseudotyped retroviral vectors |
US20060159689A1 (en) | 2004-06-17 | 2006-07-20 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
US20060008468A1 (en) | 2004-06-17 | 2006-01-12 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
US7323682B2 (en) * | 2004-07-02 | 2008-01-29 | Thermo Finnigan Llc | Pulsed ion source for quadrupole mass spectrometer and method |
US8518403B2 (en) | 2004-07-16 | 2013-08-27 | Amgen Research (Munich) Gmbh | Expression-enhanced polypeptides |
US20100111856A1 (en) | 2004-09-23 | 2010-05-06 | Herman Gill | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
EP1791565B1 (en) | 2004-09-23 | 2016-04-20 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
GB0422431D0 (en) * | 2004-10-08 | 2004-11-10 | Affitech As | Method |
US7947839B2 (en) | 2004-12-01 | 2011-05-24 | Genentech, Inc. | Heterocyclic-substituted bis-1,8 naphthalimide compounds, antibody drug conjugates, and methods of use |
US20070134243A1 (en) | 2004-12-01 | 2007-06-14 | Gazzard Lewis J | Antibody drug conjugates and methods |
CA2491067A1 (en) | 2004-12-24 | 2006-06-24 | Stichting Katholieke Universiteit | Mrna rations in urinary sediments and/or urine as a prognostic marker for prostate cancer |
WO2006112933A1 (en) | 2005-04-14 | 2006-10-26 | Agensys, Inc. | Antibodies and related molecules that bind to psca proteins |
AU2006239154A1 (en) | 2005-04-28 | 2006-11-02 | Ventana Medical Systems, Inc | Nanoparticle conjugates |
US8088908B2 (en) * | 2005-05-10 | 2012-01-03 | City Of Hope | Humanized anti-prostate stem cell antigen monoclonal antibody |
GB2426581A (en) | 2005-05-27 | 2006-11-29 | Univ Nottingham | Immunoassay methods |
DK1912675T3 (en) | 2005-07-25 | 2014-03-24 | Emergent Product Dev Seattle | B-cell reduction using specific and cd37-cd20-specific binding molecules |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
EP1942944A2 (en) | 2005-10-31 | 2008-07-16 | Genentech, Inc. | Macrocyclic depsipeptide antibody-drug conjugates and methods |
US20070212331A1 (en) | 2006-03-07 | 2007-09-13 | Baldassare Joseph J | Methods and compositions for selectively killing cells |
EP1996716B1 (en) | 2006-03-20 | 2011-05-11 | The Regents of the University of California | Engineered anti-prostate stem cell antigen (psca) antibodies for cancer targeting |
US20070286858A1 (en) | 2006-03-21 | 2007-12-13 | Wyeth | Methods and Compositions for Antagonism of RAGE |
ES2776100T3 (es) | 2006-03-31 | 2020-07-29 | Massachusetts Inst Technology | Sistema para el suministro dirigido de agentes terapéuticos |
US7566276B2 (en) | 2006-04-14 | 2009-07-28 | Dogleg Right Corporation | Multi-piece putter head having an insert |
WO2007137117A2 (en) | 2006-05-17 | 2007-11-29 | Massachusetts Institute Of Technology | Aptamer-directed drug delivery |
CN101632020B (zh) | 2006-09-13 | 2013-11-27 | 昂西免疫有限公司 | 改进的免疫测定方法 |
WO2008050255A2 (en) | 2006-10-25 | 2008-05-02 | Koninklijke Philips Electronics N. V. | Contrast agents for detecting prostate cancer |
US8362217B2 (en) | 2006-12-21 | 2013-01-29 | Emd Millipore Corporation | Purification of proteins |
WO2008079280A1 (en) | 2006-12-21 | 2008-07-03 | Millipore Corporation | Purification of proteins |
WO2008131242A1 (en) | 2007-04-18 | 2008-10-30 | Zymogenetics, Inc. | Single chain fc, methods of making and methods of treatment |
EP3023436A1 (en) | 2007-07-03 | 2016-05-25 | Dako Denmark A/S | Improved methods for generation, labeling and use of mhc multimers |
JP6126773B2 (ja) * | 2007-09-04 | 2017-05-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
WO2009039854A2 (en) | 2007-09-27 | 2009-04-02 | Dako Denmark A/S | Mhc multimers in tuberculosis diagnostics, vaccine and therapeutics |
EP2207564B1 (en) | 2007-10-18 | 2016-10-05 | Bavarian Nordic A/S | Use of mva to treat prostate cancer |
US20090169613A1 (en) | 2007-11-09 | 2009-07-02 | Reznik Boris N | Targeting of tumor stem cells through selective silencing of boris expression |
US9107858B2 (en) | 2007-12-05 | 2015-08-18 | Wisconsin Alumni Research Foundation | Dendritic cell targeting compositions and uses thereof |
ES2547552T3 (es) | 2008-02-01 | 2015-10-07 | Genentech, Inc. | Metabolito de nemorrubicina y reactivos análogos, conjugados anticuerpo-fármaco y métodos |
US8043830B2 (en) | 2008-02-01 | 2011-10-25 | The Regents Of The University Of California | Biotin-ligase system for secretion of biotinylated protein |
TW200947474A (en) | 2008-05-05 | 2009-11-16 | Ren-Huan Pan | Manufacturing equipment and method of quadratic arc alignment dua-turret formation center, and miniature milliohm current sensors manufactured thereof |
CA2720124C (en) | 2008-05-13 | 2015-07-21 | Genentech, Inc. | Analysis of antibody drug conjugates by bead-based affinity capture and mass spectrometry |
AU2009270988A1 (en) | 2008-07-15 | 2010-01-21 | Genentech, Inc. | Anthracycline derivative conjugates, process for their preparation and their use as antitumor compounds |
US20100069616A1 (en) | 2008-08-06 | 2010-03-18 | The Regents Of The University Of California | Engineered antibody-nanoparticle conjugates |
WO2010027629A2 (en) | 2008-09-08 | 2010-03-11 | Conocophillips Company | System for incondensable component separation in a liquefied natural gas facility |
WO2010037408A1 (en) | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
WO2010037397A1 (en) | 2008-10-01 | 2010-04-08 | Dako Denmark A/S | Mhc multimers in cmv immune monitoring |
RU2547600C2 (ru) | 2008-10-01 | 2015-04-10 | Эмджен Рисерч (Мьюник) Гмбх | Pscaxcd3, cd19xcd3, c-metxcd3, эндосиалинxcd3, epcamxcd3, igf-1rxcd3 или fap-альфаxcd3 биспецифическое одноцепочечное антитело с межвидовой специфичностью |
US20110318380A1 (en) | 2008-10-01 | 2011-12-29 | Dako Denmark A/S | MHC Multimers in Cancer Vaccines and Immune Monitoring |
US20110207155A1 (en) | 2008-10-13 | 2011-08-25 | Xeptagen Spa | Method for the preparation of immunoconjugates and use thereof |
CN102308004A (zh) | 2008-10-30 | 2012-01-04 | 卡里斯生命科学卢森堡控股有限责任公司 | 评价rna图案的方法 |
WO2010056337A2 (en) | 2008-11-12 | 2010-05-20 | Caris Mpi, Inc. | Methods and systems of using exosomes for determining phenotypes |
EP2358390A1 (en) | 2008-11-13 | 2011-08-24 | Emergent Product Development Seattle, LLC | Cd37 immunotherapeutic combination therapies and uses thereof |
JP2012512244A (ja) | 2008-12-16 | 2012-05-31 | イー・エム・デイー・ミリポア・コーポレイシヨン | タンパク質の精製 |
CN102265059B (zh) | 2008-12-25 | 2013-08-07 | 东海橡塑工业株式会社 | 流体封入式隔振装置 |
RU2636046C2 (ru) | 2009-01-12 | 2017-11-17 | Сайтомкс Терапьютикс, Инк | Композиции модифицированных антител, способы их получения и применения |
WO2010102195A2 (en) | 2009-03-06 | 2010-09-10 | The Johns Hopkins University | Annexin a11 and associated genes as biomarkers for cancer |
WO2010111388A2 (en) | 2009-03-24 | 2010-09-30 | Biocept, Inc. | Devices and methods of cell capture and analysis |
CN102459346B (zh) | 2009-04-27 | 2016-10-26 | 昂考梅德药品有限公司 | 制造异源多聚体分子的方法 |
MA33381B1 (fr) | 2009-05-28 | 2012-06-01 | Glaxo Group Ltd | Proteine de liaison a il-13 |
EP2448966B1 (en) | 2009-07-03 | 2018-11-14 | Avipep Pty Ltd | Immuno-conjugates and methods for producing them |
TWM383852U (en) | 2009-07-13 | 2010-07-01 | Speedtech Corp | An improvement of the universal serial bus connector |
WO2011043061A1 (ja) | 2009-10-05 | 2011-04-14 | キヤノン株式会社 | 光音響イメージング用造影剤、及び、それを用いた光音響イメージング方法 |
CA2782333C (en) | 2009-12-02 | 2019-06-04 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
US20110142811A1 (en) | 2009-12-16 | 2011-06-16 | Deutsches Krebsforschungszentrum | Measles virus for the elimination of unwanted cell populations |
CA2784610C (en) | 2009-12-23 | 2020-07-14 | Avipep Pty Ltd | Immuno-conjugates and methods for producing them |
SI2519543T1 (sl) | 2009-12-29 | 2016-08-31 | Emergent Product Development Seattle, Llc | Beljakovine, ki se vežejo s heterodimeri in njihova uporaba |
JP5808349B2 (ja) | 2010-03-01 | 2015-11-10 | カリス ライフ サイエンシズ スウィッツァーランド ホールディングスゲーエムベーハー | セラノーシスのためのバイオマーカー |
-
2008
- 2008-09-04 JP JP2010524150A patent/JP6126773B2/ja active Active
- 2008-09-04 CA CA2698343A patent/CA2698343C/en active Active
- 2008-09-04 EP EP08799192A patent/EP2197491A4/en not_active Ceased
- 2008-09-04 WO PCT/US2008/075291 patent/WO2009032949A2/en active Application Filing
- 2008-09-04 US US12/676,348 patent/US8940298B2/en active Active
-
2014
- 2014-09-12 JP JP2014186846A patent/JP6120819B2/ja active Active
- 2014-12-05 US US14/562,269 patent/US9527919B2/en active Active
-
2017
- 2017-03-28 JP JP2017062817A patent/JP2017158554A/ja active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017158554A (ja) * | 2007-09-04 | 2017-09-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 |
Also Published As
Publication number | Publication date |
---|---|
WO2009032949A2 (en) | 2009-03-12 |
EP2197491A4 (en) | 2011-01-12 |
CA2698343A1 (en) | 2009-03-12 |
US20100297004A1 (en) | 2010-11-25 |
CA2698343C (en) | 2018-06-12 |
JP2015015960A (ja) | 2015-01-29 |
JP2017158554A (ja) | 2017-09-14 |
JP6126773B2 (ja) | 2017-05-10 |
EP2197491A2 (en) | 2010-06-23 |
US9527919B2 (en) | 2016-12-27 |
US20150239983A1 (en) | 2015-08-27 |
JP2010538080A (ja) | 2010-12-09 |
WO2009032949A3 (en) | 2009-12-30 |
US8940298B2 (en) | 2015-01-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6120819B2 (ja) | 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原(psca)抗体 | |
RU2673908C2 (ru) | Мини-антитела j591 и цис-диатела для направленной доставки простата-специфичного мембранного антигена (psma) человека и способы их применения | |
US8779102B2 (en) | Recognition molecules for the treatment and detection of tumors | |
CN115960230A (zh) | 靶向分子的抗原结合构建体 | |
JP2008509656A (ja) | Tag−72に対するヒト化モノクローナル抗体 | |
JP6233933B2 (ja) | 葉酸リセプターα及びβを認識する抗体 | |
US8835167B2 (en) | Humanized anti-tag 72 CC49 for diagnosis and therapy of human tumors | |
CN104768563B (zh) | 与炎性肠病有关的抗原 | |
JP2010538080A5 (ja) | ||
KR101820029B1 (ko) | 암의 예방 및/또는 치료에서 사용하기 위한 방사성 표지 항체 단편 | |
JP5881085B2 (ja) | 膵臓癌の治療用及び診断用の組成物 | |
US20150071853A1 (en) | Nucleotide and protein sequences of an antibody directed against an epitope common to human acidic and basic ferritins, monoclonal antibodies or antibody-like molecules comprising these sequences and use thereof | |
WO2023165142A1 (zh) | Her2结合多肽及其用途 | |
US20230181772A1 (en) | Engineered anti-prostate stem cell antigen fusion proteins and uses thereof | |
Milenic | Antibody Engineering: Optimizing the delivery vehicle | |
WO2023227644A2 (en) | Binding protein | |
JP2010526108A (ja) | 癌性疾患修飾抗体 | |
CA2696634A1 (en) | Monoclonal antibodies against human acidic and basic ferritins and nucleotide and amino acid sequences thereof | |
Dearling et al. | Immunoscintigraphy and Radioimmunotherapy | |
Casey | Investigation of the effect of physical parameters on the design of tumour targeting agents | |
IL165752A (en) | Chimeric monoclonal antibody pam4, a conjugate comprising it and an antibody comprising the same or fragments thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20151013 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151222 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160205 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160413 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160607 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160906 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161206 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170131 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170302 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170328 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6120819 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |