JP6815331B2 - 前立腺がんの分析のための組成物及び方法 - Google Patents
前立腺がんの分析のための組成物及び方法 Download PDFInfo
- Publication number
- JP6815331B2 JP6815331B2 JP2017555480A JP2017555480A JP6815331B2 JP 6815331 B2 JP6815331 B2 JP 6815331B2 JP 2017555480 A JP2017555480 A JP 2017555480A JP 2017555480 A JP2017555480 A JP 2017555480A JP 6815331 B2 JP6815331 B2 JP 6815331B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- steap1
- ctc
- prostate
- cells
- 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
- 238000000034 method Methods 0.000 title claims description 82
- 208000000236 Prostatic Neoplasms Diseases 0.000 title claims description 57
- 206010060862 Prostate cancer Diseases 0.000 title claims description 55
- 239000000203 mixture Substances 0.000 title claims description 38
- 238000004458 analytical method Methods 0.000 title description 7
- 210000004027 cell Anatomy 0.000 claims description 191
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 claims description 116
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 claims description 116
- 210000002307 prostate Anatomy 0.000 claims description 66
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 60
- 238000011282 treatment Methods 0.000 claims description 56
- 230000014509 gene expression Effects 0.000 claims description 52
- 210000004369 blood Anatomy 0.000 claims description 40
- 239000008280 blood Substances 0.000 claims description 40
- 239000003550 marker Substances 0.000 claims description 37
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 claims description 36
- 230000003321 amplification Effects 0.000 claims description 32
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 32
- 102000011782 Keratins Human genes 0.000 claims description 31
- 108010076876 Keratins Proteins 0.000 claims description 31
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 25
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 25
- 238000002560 therapeutic procedure Methods 0.000 claims description 20
- 239000000611 antibody drug conjugate Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 210000004408 hybridoma Anatomy 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 11
- 238000000116 DAPI staining Methods 0.000 claims description 10
- 229940127089 cytotoxic agent Drugs 0.000 claims description 10
- 230000004044 response Effects 0.000 claims description 10
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 claims description 9
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims description 9
- 108010093470 monomethyl auristatin E Proteins 0.000 claims description 8
- 238000010186 staining Methods 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 239000002254 cytotoxic agent Substances 0.000 claims description 7
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 7
- 230000000813 microbial effect Effects 0.000 claims description 7
- 238000012544 monitoring process Methods 0.000 claims description 7
- 239000003053 toxin Substances 0.000 claims description 5
- 231100000765 toxin Toxicity 0.000 claims description 5
- 108700012359 toxins Proteins 0.000 claims description 5
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 3
- 238000003364 immunohistochemistry Methods 0.000 claims description 3
- 230000001293 nucleolytic effect Effects 0.000 claims description 2
- 210000005266 circulating tumour cell Anatomy 0.000 claims 22
- 230000002708 enhancing effect Effects 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 description 138
- 201000011510 cancer Diseases 0.000 description 107
- 239000000427 antigen Substances 0.000 description 37
- 108091007433 antigens Proteins 0.000 description 36
- 102000036639 antigens Human genes 0.000 description 36
- 230000027455 binding Effects 0.000 description 31
- 239000003446 ligand Substances 0.000 description 28
- 150000007523 nucleic acids Chemical class 0.000 description 27
- 108020004707 nucleic acids Proteins 0.000 description 26
- 102000039446 nucleic acids Human genes 0.000 description 26
- 238000003556 assay Methods 0.000 description 25
- 239000000523 sample Substances 0.000 description 25
- 102100038358 Prostate-specific antigen Human genes 0.000 description 18
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 17
- 238000001514 detection method Methods 0.000 description 17
- 239000006249 magnetic particle Substances 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- 210000000265 leukocyte Anatomy 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 14
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 14
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 11
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 239000000975 dye Substances 0.000 description 10
- 206010027476 Metastases Diseases 0.000 description 9
- 125000003275 alpha amino acid group Chemical group 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 238000001574 biopsy Methods 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 239000012634 fragment Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000009401 metastasis Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- -1 testicle removal Substances 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000004393 prognosis Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 238000012875 competitive assay Methods 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 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 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 4
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000001354 painful effect Effects 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000000049 pigment Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- 101710120463 Prostate stem cell antigen Proteins 0.000 description 3
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 208000026487 Triploidy Diseases 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000000562 conjugate Substances 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000005484 gravity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000007901 in situ hybridization Methods 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000092 prognostic biomarker Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 208000023958 prostate neoplasm Diseases 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 208000024891 symptom Diseases 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
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- AUUIARVPJHGTSA-UHFFFAOYSA-N 3-(aminomethyl)chromen-2-one Chemical compound C1=CC=C2OC(=O)C(CN)=CC2=C1 AUUIARVPJHGTSA-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 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 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000001815 biotherapy Methods 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 239000010415 colloidal nanoparticle Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000004163 cytometry Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000007885 magnetic separation Methods 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 2
- 238000011471 prostatectomy Methods 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- RWRDJVNMSZYMDV-SIUYXFDKSA-L (223)RaCl2 Chemical compound Cl[223Ra]Cl RWRDJVNMSZYMDV-SIUYXFDKSA-L 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- 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 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 101100519151 Arabidopsis thaliana CEP10 gene Proteins 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010015133 Galactose oxidase Proteins 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 206010056740 Genital discharge Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 1
- 101000605534 Homo sapiens Prostate-specific antigen Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 102100038609 Lactoperoxidase Human genes 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- SGDBTWWWUNNDEQ-UHFFFAOYSA-N Merphalan Chemical compound OC(=O)C(N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-UHFFFAOYSA-N 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 241000609499 Palicourea Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 108010092464 Urate Oxidase Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 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 description 1
- 241000700605 Viruses Species 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N Xanthine Natural products O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 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 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- NLEBIOOXCVAHBD-QKMCSOCLSA-N dodecyl beta-D-maltoside Chemical compound O[C@@H]1[C@@H](O)[C@H](OCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLEBIOOXCVAHBD-QKMCSOCLSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 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 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 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
- 210000005265 lung cell Anatomy 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 108010029942 microperoxidase Proteins 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940092814 radium (223ra) dichloride Drugs 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 102220005400 rs34324664 Human genes 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 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 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 description 1
- 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 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6871—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting an enzyme
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
-
- 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
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4742—Keratin; Cytokeratin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70589—CD45
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/902—Oxidoreductases (1.)
- G01N2333/90287—Oxidoreductases (1.) oxidising metal ions (1.16)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Description
本出願は、2015年4月21日出願の米国仮出願第62/150724号の優先権の利益を主張し、この出願はその全体が参照により本明細書に援用される。
本明細書において交換可能に使用される用語「腫瘍」又は「がん」は、腫瘍性又は悪性の細胞の成長、増殖、又は転移を特徴とするいずれかの医学的状態を指し、固形がん及び白血病などの非固形がんの両方を含む。
本明細書に開示される方法は、侵襲的、外科的生検を行うことなく、STEAP1−ADC療法の恩恵を受けるであろう患者を同定することができ、且つ疾患の進行とSTEAP1−ADC療法の有効性を監視することができるという未だ満たされていない需要を満たす。この方法は、侵襲性で痛みを伴う生検を行うことなく、STEAP1−ADC療法のよい候補となる患者及びSTEAP1−ADC療法に応答するであろう患者の検出及び選択を可能にする。またこの方法は、STEAP1−ADCによる治療の間に、STEAP1+CTC及びSTEAP1の発現を頻繁に監視することを可能にする。頻繁な監視により、外科的生検ではその侵襲性により可能でない、用量調節及び個別化が可能となる。したがって、本明細書に開示される方法は、ADC治療法が特異的バイオマーカーに焦点を当てたものであり、その特異的バイオマーカーのレベルを、ADC療法の前、最中及び後に監視及び検出することができると有利であるため、ADC療法のために特に重要である。
別の態様では、本発明は、抗体15A5が結合するのと実質的に同じエピトープに結合する抗体を提供し、抗体15A5は、微生物寄託番号PTA−12259を有するハイブリドーマ細胞により生成される。
抗体は、例えば米国特許第4816567号に記載されているような組み換え方法及び組成物を用いて生成することができる。一実施態様では、本明細書に記載される抗STEAP−1抗体をコードする単離された核酸が提供される。このような核酸は、抗体のVLを含むアミノ酸配列、及び/又は抗体のVHを含むアミノ酸配列(例えば、抗体の軽鎖及び/又は重鎖)をコードしうる。さらなる実施態様では、そのような核酸を含む一又は複数のベクター(例えば、発現ベクター)が提供される。さらなる実施態様では、そのような核酸を含む宿主細胞が提供される。このような一実施態様では、宿主細胞は:(1)抗体のVLを含むアミノ酸配列及び抗体のVHを含むアミノ酸配列をコードする核酸を含むベクター、又は(2)抗体のVLを含むアミノ酸配列をコードする核酸を含む第一ベクター及び抗体のVHを含むアミノ酸配列をコードする核酸を含む第ニベクターを含む(例えば、同ベクターで形質転換されている)。一実施態様において、宿主細胞は、真核生物細胞、例えばチャイニーズハムスター卵巣(CHO)細胞、又はリンパ系細胞(例えば、Y0、NS0、Sp20細胞)である。一実施態様において、上述のように、抗体の発現に適した条件下で、抗体をコードする核酸を含む宿主細胞を培養することと、任意選択的に宿主細胞(又は宿主細胞培地)から抗体を回収することとを含む、抗STEAP−1抗体を作製する方法が提供される。
本明細書において提供される抗体は、前立腺がんの診断試薬の製造に使用することができる。抗体は、診断目的に適した検出可能標識とさらにコンジュゲートし、適切な形態、例えば凍結乾燥させた粉末で、又は適切な溶液の形態で提供される。
本発明の別の態様では、前立腺ガンの診断又は予後予測に有用な組成物を含むテストキットが提供される。
以下は、本発明の方法及び組成物の実施例である。上に提供された一般的な説明を前提として、他の様々な実施態様が実施されうることが理解される。
この実施例に示されるように、免疫蛍光に基づくアッセイは、CTCの表面上におけるSTEAP1の頑強な検出と、治療後のCTCの総数並びにSTEAP1+CTCの減少とを実証することができた。
進行性mCRPCを有する60名の患者は、0.3から2.8mg/kgの範囲のSTEAP1−ADCを、三週に一度投与された。ADC活性を、PSAの減少により、>6ヶ月の研究時間において測定した。≧2mg/kgの用量において、≧50%のPSAの減少が、10/45名(22%±12.1)の患者に観察された。ADC活性は、IHC 3+腫瘍を有する患者において最も顕著であった。≧2mg/kgにおいて、20/45名の患者(44%±14.5)が、ベースラインにおいて7.5mL当たり≧5という望ましくないCTC数を有しており、評価可能と考慮された。1回目の治療サイクル後、望ましくない数から望ましい数へのCTC変換が11/20名の患者(55%±21.8)に見られ、PSA減少と有意に相関していた(スピアマンの順位r=0.74)。CTCは、FACSにより、14/29の試料(49%±31−66%)において、EpCAM+/CD45−イベントに容易に検出可能なSTEAP1+シグナルを示した。STEAP1+イベントは、0〜74%の範囲のEpCAM+/CD45−特性を示し、FACSでソートされたEpCAM+/CD45−イベントは、前立腺がんの推定マーカーAR及びKLK3に沿ってSTEAP1+RT−PCR発現を示した。EPICにより、STEAP1は18/42の試料(43%±14.98)に検出され、範囲はSTEAP1+CTCの1〜56%であった。治療後、ベースラインと比較して、STEAP1+の患者の割合の減少と、STEAP1=CTCの増加が観察された。17名の患者がSTEAP1 PET試験に参加した。STEAP1−ADCで治療した14名の患者のうち、4/14名(29%±12〜55%)の患者においてPSAに≧50%の減少があった。治療時間は骨転移SUVmaxと相関していた(r=0.63)。高いSUV転移の8のPET誘導生検すべてでSTEAP1 IHC 2+/3+が確認された。
STEAP1シグナルを、SKBR3(STEAP1ネガティブコントロール)及びLnCaP(STEAP1ポジティブコントロール)前立腺がん細胞株において、増幅プロトコールの存在下及び非存在下において測定した(図9)。STEAP+試料のカットオフはそれぞれ、非増幅プロトコールを用いた場合>3のシグナル、増幅プロトコールを用いた場合>8のシグナルであった。非増幅プロトコールは、LnCaP(ポジティブコントロール)細胞株にSKBR3(ネガティブコントロール)細胞株の7.6倍のシグナル増加を示した。増幅プロトコールは、LnCaP(ポジティブコントロール)細胞株にSKBR3(ネガティブコントロール)細胞株の25倍のシグナル増加を示した(図9A)。STEAP1シグナルを増幅した結果、LnCaP(ポジティブコントロール)細胞株の平均STEAP1シグナルが8.1倍に増加したが、背景(即ち、SKBR3ネガティブコントロールシグナル)の増加はわずか2.4倍であった(図9A)。
血液試料を、STEAP1−ADCによる治療の前、最中、及び後に採取した。図10に示すように、治療が進行するにつれ、STEAP1+CTCの数は減少した。
Claims (13)
- 循環性腫瘍細胞(CTC)を用いて被験者の前立腺がんを診断するための方法であって:
a)CTCの濃縮なく、被験者から採取された血液試料由来のCTCを含む組成物を取得すること;
b)CTCを含む組成物を、STEAP1に特異的に結合する抗体、CD45に特異的に結合する抗体、及びサイトケラチンに特異的に結合する抗体と接触させること;
c)CTCをDAPIで染色すること;並びに
d)DAPI染色及び結合した抗体を検出することであって、STEAP1に結合した抗STEAP1抗体が、シグナルを強化するためのチラミドシグナル増幅(TSA)プロトコールを用いて検出される、検出すること、を含み、且つ
サイトケラチン及びSTEAP1を発現し、DAPI染色を呈し、且つCD45を発現しないCTCの存在により、被験者が前立腺がんを有することが予測される、方法。 - 抗STEAP1抗体が、微生物寄託番号PTA−12259を有するハイブリドーマ細胞により生成される15A5抗体である、請求項1に記載の方法。
- CTC上のSTEAP1の発現レベルを決定することをさらに含む、請求項1又は2に記載の方法。
- STEAP1の発現レベルに基づいてCTCをグレード付けすること、及び各グレードのCTCのパーセンテージを決定することをさらに含む、請求項1から3のいずれか一項に記載の方法。
- 各グレードのグレードスコアを、前記グレードのCTCのパーセンテージに、前記グレードの前立腺特異的マーカーの発現レベルを表す固有のグレード数を乗じることにより計算すること、及びすべてのグレードスコアを合算してHスコアを取得することをさらに含み、Hスコアにより被験者の前立腺がんのステージが示される、請求項1から4のいずれか一項に記載の方法。
- 抗STEAP−1抗体が、≦1000nMのKDでSTEAP−1に結合する、請求項1から5のいずれか一項に記載の方法。
- 抗STEAP−1抗体、抗CD45抗体、及び/又は抗サイトケラチン抗体が、検出可能な標識にコンジュゲートされる、請求項1から6のいずれか一項に記載の方法。
- 前立腺がんに罹患している被験者におけるSTEAP1−抗体薬物コンジュゲート(ADC)療法の有効性を予測する方法であって:
a)CTCの濃縮なく、被験者から採取された血液試料由来のCTCを含む組成物を取得すること;
b)CTCを含む組成物を、STEAP1に特異的に結合する抗体、CD45に特異的に結合する抗体、及びサイトケラチンに特異的に結合する抗体と接触させること;
c)CTCをDAPIで染色すること;並びに
d)DAPI染色及び結合した抗体を検出することであって、STEAP1に結合した抗STEAP1抗体が、シグナルを強化するためのチラミドシグナル増幅(TSA)プロトコールを用いて検出される、検出すること、を含み、且つ
サイトケラチン及びSTEAP1を発現し、DAPI染色を呈し、且つCD45を発現しないCTCの存在により、STEAP1−ADCの有効性が予測される、方法。 - 前立腺がんに罹患している被験者におけるSTEAP1−ADC療法への応答を、シグナルを強化するためのチラミドシグナル増幅(TSA)プロトコールを用いて監視する方法であって:
a)CTCを含む第1の組成物を、STEAP1に特異的に結合する抗体、CD45に特異的に結合する抗体、及びサイトケラチンに特異的に結合する抗体と接触させること並びに細胞をDAPIで染色することであって、CTCを含む第1の組成物が、STEAP1−ADCによる治療前に被験者から採取された第1の血液試料からCTCの濃縮なく取得されるものである、こと;
b)STEAP1及びサイトケラチンを発現し、DAPIで染色され、CD45を発現しない第1の組成物中のCTCの数を決定すること;
c)CTCを含む第2の組成物を、STEAP1に特異的に結合する抗体、CD45に特異的に結合する抗体、及びサイトケラチンに特異的に結合する抗体と接触させること並びに細胞をDAPIで染色することであって、CTCを含む第2の組成物が、CTCの濃縮なくSTEAP1−ADCによる治療の間に又は後で被験者から採取された第2の血液試料から取得されるものである、こと;
d)STEAP1及びサイトケラチンを発現し、DAPIで染色され、CD45を発現しいない第2の組成物中のCTCの量を決定すること;及び
e)b)で決定されたCTCの量を、d)で決定されたものと比較すること、
を含み、
CTCの量の減少により、被験者における前立腺がん治療法への応答が示される、方法。 - STEAP1−ADCが、細胞傷害性剤に共有結合する抗STEAP1抗体を含む、請求項8又は9に記載の方法。
- 細胞傷害性剤が、毒素、化学療法剤、薬物部分、モノメチルアウリスタチンE(MMAE)、抗生物質、放射性同位体、及び核酸分解酵素から選択される、請求項10に記載の方法。
- DAPI、STEAP1、CD45、及びサイトケラチンのシグナルが、FACSを用いて検出される、請求項1から11のいずれか一項に記載の方法。
- DAPI、STEAP1、CD45、及びサイトケラチンのシグナルが、免疫組織化学を用いて検出される、請求項1から11のいずれか一項に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562150724P | 2015-04-21 | 2015-04-21 | |
US62/150,724 | 2015-04-21 | ||
PCT/US2016/028372 WO2016172160A1 (en) | 2015-04-21 | 2016-04-20 | Compositions and methods for prostate cancer analysis |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020212062A Division JP7022191B2 (ja) | 2015-04-21 | 2020-12-22 | 前立腺がんの分析のための組成物及び方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018517129A JP2018517129A (ja) | 2018-06-28 |
JP6815331B2 true JP6815331B2 (ja) | 2021-01-20 |
Family
ID=55969465
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017555480A Active JP6815331B2 (ja) | 2015-04-21 | 2016-04-20 | 前立腺がんの分析のための組成物及び方法 |
JP2020212062A Active JP7022191B2 (ja) | 2015-04-21 | 2020-12-22 | 前立腺がんの分析のための組成物及び方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020212062A Active JP7022191B2 (ja) | 2015-04-21 | 2020-12-22 | 前立腺がんの分析のための組成物及び方法 |
Country Status (5)
Country | Link |
---|---|
US (2) | US20180209982A1 (ja) |
EP (1) | EP3286565A1 (ja) |
JP (2) | JP6815331B2 (ja) |
CN (2) | CN113552350A (ja) |
WO (1) | WO2016172160A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3817770A2 (en) | 2018-07-02 | 2021-05-12 | Amgen Inc. | Anti-steap1 antigen-binding protein |
JP2020071152A (ja) | 2018-10-31 | 2020-05-07 | ソニー株式会社 | 免疫染色方法、免疫染色システム、および免疫染色キット |
JP2021018154A (ja) * | 2019-07-22 | 2021-02-15 | 学校法人杏林学園 | 腫瘍細胞クラスタの検出方法、及び腫瘍細胞クラスタの回収方法、並びに、それらの方法に用いる試薬及び担体固定化分子 |
JP2022546572A (ja) * | 2019-09-05 | 2022-11-04 | メモリアル スローン ケタリング キャンサー センター | 抗steap1抗体およびその使用 |
BR102020013625A2 (pt) * | 2020-07-02 | 2022-01-11 | Universidade Federal de Uberlândia | Aptâmero modificado, sistema aptaimunológico, painel aptaimunológico, kit, método e uso no diagnóstico de câncer de próstata |
KR102423482B1 (ko) * | 2020-08-12 | 2022-07-22 | 인제대학교 산학협력단 | 혈중암세포를 분리하는 장치 및 이를 이용한 암의 진단 또는 예후에 필요한 정보를 제공하는 방법 |
CN114729055B (zh) * | 2022-02-24 | 2023-01-24 | 青岛华赛伯曼医学细胞生物有限公司 | 共表达CD45和EpCAM的细胞群的检测和分离方法及其用途 |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
US5597531A (en) | 1985-10-04 | 1997-01-28 | Immunivest Corporation | Resuspendable coated magnetic particles and stable magnetic particle suspensions |
JP2919890B2 (ja) | 1988-11-11 | 1999-07-19 | メディカル リサーチ カウンスル | 単一ドメインリガンド、そのリガンドからなる受容体、その製造方法、ならびにそのリガンドおよび受容体の使用 |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5698271A (en) | 1989-08-22 | 1997-12-16 | Immunivest Corporation | Methods for the manufacture of magnetically responsive particles |
US5959177A (en) | 1989-10-27 | 1999-09-28 | The Scripps Research Institute | Transgenic plants expressing assembled secretory antibodies |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
WO1993006217A1 (en) | 1991-09-19 | 1993-04-01 | Genentech, Inc. | EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
EP1997894B1 (en) | 1992-02-06 | 2011-03-30 | Novartis Vaccines and Diagnostics, Inc. | Biosynthetic binding protein for cancer marker |
US5789199A (en) | 1994-11-03 | 1998-08-04 | Genentech, Inc. | Process for bacterial production of polypeptides |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5994071A (en) | 1997-04-04 | 1999-11-30 | Albany Medical College | Assessment of prostate cancer |
US6040498A (en) | 1998-08-11 | 2000-03-21 | North Caroline State University | Genetically engineered duckweed |
WO1999041613A1 (en) | 1998-02-12 | 1999-08-19 | Immunivest | Methods and reagents for the rapid and efficient isolation of circulating cancer cells |
US7125978B1 (en) | 1999-10-04 | 2006-10-24 | Medicago Inc. | Promoter for regulating expression of foreign genes |
MXPA02003456A (es) | 1999-10-04 | 2002-10-23 | Medicago Inc | Metodo para regular la transcripcion de genes foraneos. |
ATE489452T1 (de) * | 2003-02-27 | 2010-12-15 | Veridex Llc | Zirkulierende tumorzellen (ctc's): frühe beurteilung von time-to-progression, überleben und ansprechen auf therapie bei patienten mit metastasiertem krebs |
CN101018874A (zh) * | 2004-08-13 | 2007-08-15 | 千年药品公司 | 用于鉴定、评估、预防和治疗***癌的基因、组合物、试剂盒和方法 |
NZ580115A (en) * | 2004-09-23 | 2010-10-29 | Genentech Inc | Cysteine engineered antibody light chains and conjugates |
KR20090111307A (ko) * | 2006-07-03 | 2009-10-26 | 엑손히트 써라퓨틱스 에스에이 | 전립선 특이적 전사물 및 전립선암의 치료 및 진단에 사용되는 이의 용도 |
WO2011008990A1 (en) * | 2009-07-15 | 2011-01-20 | Prometheus Laboratories Inc. | Drug selection for gastric cancer therapy using antibody-based arrays |
ES2390083T3 (es) * | 2007-01-16 | 2012-11-06 | Musc Foundation For Research Development | Composiciones y procedimientos para diagnosticar, tratar y prevenir afecciones de próstata |
AR070047A1 (es) * | 2007-12-27 | 2010-03-10 | Infinity Pharmaceuticals Inc | Tratamientos terapeuticos contra el cancer. composicion que comprende un inhibidor de hedgehog. |
JP2011512125A (ja) * | 2008-02-01 | 2011-04-21 | 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 | マイクロ流体画像サイトメトリ |
IT1391619B1 (it) * | 2008-11-04 | 2012-01-11 | Silicon Biosystems Spa | Metodo per l'individuazione, selezione e analisi di cellule tumorali |
EP3045918B1 (en) * | 2009-10-21 | 2017-12-06 | The Scripps Research Institute | Method of using non-rare cells to detect rare cells |
WO2011063416A2 (en) * | 2009-11-23 | 2011-05-26 | The General Hospital Corporation | Microfluidic devices for the capture of biological sample components |
CN101943703A (zh) * | 2010-06-28 | 2011-01-12 | 首都医科大学 | 一种基于纳米技术的微量蛋白质检测方法 |
US20140235495A1 (en) * | 2011-09-23 | 2014-08-21 | Siemens Healthcare Diagnostics Inc. | Cell response assay for cancer and methods of producing and using same |
US20130143237A1 (en) * | 2011-11-29 | 2013-06-06 | Genentech, Inc. | Compositions and methods for prostate cancer analysis |
CN102492772A (zh) * | 2011-12-02 | 2012-06-13 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 一种分子检测信号放大技术 |
WO2013086031A1 (en) * | 2011-12-05 | 2013-06-13 | Nestec S.A. | Method of therapy selection for patients with cancer |
CN104428677A (zh) * | 2011-12-09 | 2015-03-18 | 斯克利普斯研究所 | 用于识别循环肿瘤细胞的设备、***和方法 |
ES2695101T3 (es) * | 2011-12-30 | 2019-01-02 | Ventana Med Syst Inc | Análisis automatizado de células tumorales circulantes |
CN110055325A (zh) * | 2011-12-30 | 2019-07-26 | 雅培分子公司 | 用于***癌的诊断、预后和评估治疗性/预防性治疗的材料和方法 |
JP6254951B2 (ja) * | 2012-01-24 | 2017-12-27 | ファイザー・インク | 哺乳類の対象における5t4陽性循環腫瘍細胞を検出するための方法および5t4陽性がんの診断の方法 |
CN103792364B (zh) * | 2012-10-31 | 2016-06-08 | 张宝弘 | 用于检测外周血中循环肿瘤细胞ror1蛋白的试剂及其应用 |
CN105102978B (zh) * | 2013-02-02 | 2018-11-02 | 杜克大学 | 分离循环肿瘤细胞的方法 |
CN106062561B (zh) * | 2013-09-30 | 2021-11-09 | 斯克利普斯研究院 | 为了监测***癌患者中的肿瘤进化进行循环肿瘤细胞的基因型和表型分析 |
EP2883962B1 (en) * | 2013-12-16 | 2017-09-13 | Humanitas Mirasole S.p.A. | High levels of EMT-TFs for the diagnosis of cancer, in particular of colorectal (CRC) and pancreatic (PC) cancer |
EP3132267B1 (en) * | 2014-04-17 | 2019-08-14 | Siemens Healthcare Diagnostics Inc. | Method to screen out false positives in a circulating tumor cell assay |
-
2016
- 2016-04-20 EP EP16722737.0A patent/EP3286565A1/en active Pending
- 2016-04-20 WO PCT/US2016/028372 patent/WO2016172160A1/en active Application Filing
- 2016-04-20 CN CN202110510659.1A patent/CN113552350A/zh active Pending
- 2016-04-20 JP JP2017555480A patent/JP6815331B2/ja active Active
- 2016-04-20 CN CN201680029704.9A patent/CN108064343B/zh active Active
-
2017
- 2017-10-20 US US15/789,768 patent/US20180209982A1/en not_active Abandoned
-
2019
- 2019-12-19 US US16/721,108 patent/US20200200752A1/en active Pending
-
2020
- 2020-12-22 JP JP2020212062A patent/JP7022191B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2021073437A (ja) | 2021-05-13 |
US20180209982A1 (en) | 2018-07-26 |
US20200200752A1 (en) | 2020-06-25 |
JP2018517129A (ja) | 2018-06-28 |
CN108064343A (zh) | 2018-05-22 |
JP7022191B2 (ja) | 2022-02-17 |
WO2016172160A1 (en) | 2016-10-27 |
EP3286565A1 (en) | 2018-02-28 |
CN113552350A (zh) | 2021-10-26 |
CN108064343B (zh) | 2021-07-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7022191B2 (ja) | 前立腺がんの分析のための組成物及び方法 | |
EP3130605B1 (en) | Folate receptor alpha as a diagnostic and prognostic marker for folate receptor alpha-expressing cancers | |
US9632091B2 (en) | Compositions and methods for prostate cancer analysis | |
JP2011517341A (ja) | 小細胞肺癌バイオマーカーパネル | |
JP6239503B2 (ja) | 新規な抗cxcr4抗体並びに癌の検出および診断のためのその使用 | |
JP2010535710A (ja) | 細胞増殖性疾患の検出及び診断に有用なigf−1r特異抗体 | |
AU2017204043A1 (en) | Use of the antibody I-3859 for the detection and diagnosis of cancer | |
JP6940505B2 (ja) | 組成物および癌の発生リスクの評価方法 | |
US20130136689A1 (en) | Proteins | |
JP2020143122A (ja) | Igf−1r抗体および癌の診断のためのその使用 | |
JP6312700B2 (ja) | 膀胱癌中のpodxl | |
WO2021030450A1 (en) | Novel lox-1 antibody compositions, lox1 neutralization assay and methods of treatment using same | |
CN107709362B (zh) | Igf-1r抗体及其用于癌症诊断的用途 | |
Shively et al. | The XXXIVth Meeting of the International Society for Oncodevelopmental Biology and Medicine, ISOBM 2006 September 16–20, 2006, Pasadena, Calif. | |
WO2014079954A1 (en) | Methods of diagnosing and therapeutic agents for use in the treatment of cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190418 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200129 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200303 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200603 |
|
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: 20201208 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201222 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6815331 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |