JP4904266B2 - 抗−tf−抗原抗体の治療的使用 - Google Patents
抗−tf−抗原抗体の治療的使用 Download PDFInfo
- Publication number
- JP4904266B2 JP4904266B2 JP2007523692A JP2007523692A JP4904266B2 JP 4904266 B2 JP4904266 B2 JP 4904266B2 JP 2007523692 A JP2007523692 A JP 2007523692A JP 2007523692 A JP2007523692 A JP 2007523692A JP 4904266 B2 JP4904266 B2 JP 4904266B2
- Authority
- JP
- Japan
- Prior art keywords
- jaa
- composition
- cells
- group
- cancer 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.)
- Expired - Fee Related
Links
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 59
- 206010027476 Metastases Diseases 0.000 claims description 29
- 201000011510 cancer Diseases 0.000 claims description 27
- 230000009401 metastasis Effects 0.000 claims description 27
- 206010006187 Breast cancer Diseases 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 208000026310 Breast neoplasm Diseases 0.000 claims description 15
- 239000012634 fragment Substances 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 239000002246 antineoplastic agent Substances 0.000 claims description 13
- 229940127089 cytotoxic agent Drugs 0.000 claims description 13
- 230000002285 radioactive effect Effects 0.000 claims description 10
- 239000003053 toxin Substances 0.000 claims description 7
- 231100000765 toxin Toxicity 0.000 claims description 7
- 108700012359 toxins Proteins 0.000 claims description 7
- 230000035755 proliferation Effects 0.000 claims description 6
- 230000012010 growth Effects 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 108010039491 Ricin Proteins 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 206010013023 diphtheria Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 210000004027 cell Anatomy 0.000 description 95
- QCQYVCMYGCHVMR-AAZUGDAUSA-N n-[(2r,3r,4s,5r)-4,5,6-trihydroxy-1-oxo-3-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexan-2-yl]acetamide Chemical compound CC(=O)N[C@@H](C=O)[C@H]([C@@H](O)[C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O QCQYVCMYGCHVMR-AAZUGDAUSA-N 0.000 description 51
- 238000000034 method Methods 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 27
- 206010061289 metastatic neoplasm Diseases 0.000 description 26
- 210000004072 lung Anatomy 0.000 description 23
- 230000001394 metastastic effect Effects 0.000 description 19
- 230000003902 lesion Effects 0.000 description 17
- 230000004083 survival effect Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 201000000050 myeloid neoplasm Diseases 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000005907 cancer growth Effects 0.000 description 5
- 150000001720 carbohydrates Chemical group 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002595 magnetic resonance imaging Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000002054 transplantation Methods 0.000 description 5
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 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 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 210000001951 dura mater Anatomy 0.000 description 4
- 210000003038 endothelium Anatomy 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 102000013415 peroxidase activity proteins Human genes 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 108090001090 Lectins Proteins 0.000 description 3
- 102000004856 Lectins Human genes 0.000 description 3
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 3
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000002523 lectin Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-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
- 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
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- RJOJUSXNYCILHH-UHFFFAOYSA-N gadolinium(3+) Chemical compound [Gd+3] RJOJUSXNYCILHH-UHFFFAOYSA-N 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229940116978 human epidermal growth factor Drugs 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- -1 imide esters Chemical class 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 210000005075 mammary gland Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000004088 microvessel Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 2
- 230000024121 nodulation Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 238000005096 rolling process Methods 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- IEUUDEWWMRQUDS-UHFFFAOYSA-N (6-azaniumylidene-1,6-dimethoxyhexylidene)azanium;dichloride Chemical compound Cl.Cl.COC(=N)CCCCC(=N)OC IEUUDEWWMRQUDS-UHFFFAOYSA-N 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- YBBNVCVOACOHIG-UHFFFAOYSA-N 2,2-diamino-1,4-bis(4-azidophenyl)-3-butylbutane-1,4-dione Chemical compound C=1C=C(N=[N+]=[N-])C=CC=1C(=O)C(N)(N)C(CCCC)C(=O)C1=CC=C(N=[N+]=[N-])C=C1 YBBNVCVOACOHIG-UHFFFAOYSA-N 0.000 description 1
- CHMNMRMSFMQHGI-UHFFFAOYSA-N 2-(2,5-diphenyl-1H-tetrazol-1-ium-3-yl)-4,5-dimethyl-1,3-thiazole 2H-tetrazol-1-ium dibromide Chemical compound [Br-].[Br-].[NH2+]1C=NN=N1.S1C(C)=C(C)N=C1N1N(C=2C=CC=CC=2)[NH2+]C(C=2C=CC=CC=2)=N1 CHMNMRMSFMQHGI-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- 240000004244 Cucurbita moschata Species 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 235000009852 Cucurbita pepo Nutrition 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 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
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101710082714 Exotoxin A Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000007563 Galectins Human genes 0.000 description 1
- 108010046569 Galectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 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 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- 244000302512 Momordica charantia Species 0.000 description 1
- 235000009811 Momordica charantia Nutrition 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- RMINQIRDFIBNLE-NNRWGFCXSA-N O-[N-acetyl-alpha-neuraminyl-(2->6)-N-acetyl-alpha-D-galactosaminyl]-L-serine Chemical compound O1[C@H](OC[C@H](N)C(O)=O)[C@H](NC(=O)C)[C@@H](O)[C@@H](O)[C@H]1CO[C@@]1(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C1 RMINQIRDFIBNLE-NNRWGFCXSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101100413173 Phytolacca americana PAP2 gene Proteins 0.000 description 1
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 240000001866 Vernicia fordii Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 108010001818 alpha-sarcin Proteins 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 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
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 238000005460 biophysical method Methods 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004712 cancer cell adhesion Effects 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229930191339 dianthin Natural products 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- CEALXSHFPPCRNM-UHFFFAOYSA-L disodium;carboxylato carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OC([O-])=O CEALXSHFPPCRNM-UHFFFAOYSA-L 0.000 description 1
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010028531 enomycin Proteins 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002134 immunopathologic effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- XMBWDFGMSWQBCA-OIOBTWANSA-N iodane Chemical compound [124IH] XMBWDFGMSWQBCA-OIOBTWANSA-N 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000309715 mini pig Species 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 108010076042 phenomycin Proteins 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001184 polypeptide 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
- 230000008092 positive effect Effects 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000013777 protein digestion Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000000614 rib Anatomy 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000020354 squash Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- LZAJKCZTKKKZNT-PMNGPLLRSA-N trichothecene Chemical compound C12([C@@]3(CC[C@H]2OC2C=C(CCC23C)C)C)CO1 LZAJKCZTKKKZNT-PMNGPLLRSA-N 0.000 description 1
- 229930013292 trichothecene Natural products 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- 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
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
- A61K47/6819—Plant toxins
-
- 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
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6817—Toxins
- A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
-
- 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
- A61K47/6851—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
- A61K47/6855—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 the tumour determinant being from breast cancer cell
-
- 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
- A61K51/1045—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 against animal or human tumor cells or tumor cell determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Botany (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Peptides Or Proteins (AREA)
Description
本発明は、国立衛生研究所(the National Institutes of Health)からの登録番号R15AI49210-01により支援された。当該機関が本発明の所定の権利を有する。
TF-Agは、アルファO-セリンまたはO-トレオニン結合によりタンパク質に結合される二糖であるガラクトースβ1-3N-アセチルガラクトサミンである。TF-AgはThomsen、FriedenreichおよびHueberにより1920年代の後期に発見された(2)。TF-Agは、三次元構造によるか、または高度にネガティブに荷電したシアル酸によるかのいずれかにより他の炭水化物に連結しているので、種々の正常な細胞膜上では隠れている(3,7)。TF-Agの密度により、癌腫の組織学的グレード(9,11)、浸潤性ポテンシャル、および乳癌(2,12-13)、膀胱および前立腺癌腫(14)の早期再発の可能性が予測される。
他の態様では、個人において、TF-Agを発現する癌細胞の増殖を阻害する方法が提供される。当該方法は、TF-Agを発現している癌細胞の増殖を阻害するのに有効な量のJAA-F11 mAbsを個人に投与することを含む。
他の態様では、個人において、TF-Agを発現している転移性病巣、腫瘍またはこれらの組合せを同定するための方法が提供される。前記方法は、検出可能な標識に結合されたJAA-F11 mAbsを個人に投与するステップと、前記検出可能な標識を検出して、当該転移性病巣、腫瘍またはこれらの組合せを同定するステップを含む。
以下の実施例は本発明を説明するためのものであり、特許請求の範囲の範囲を限定することを意味しない。
本実施例により、モノクローナル抗体JAA-F11による内皮および骨髄細胞への癌細胞の接着の阻害を示す。ヒト臍帯静脈内皮細胞(HUVEC)は、カスケード・バイオロジクス(Cascade Biologics)(ポートランド、OR)から購入した。FBS(2% v/v終濃度)、ヒドロコルチソン、ヒト繊維芽細胞増殖因子、ヘパリンおよびヒト表皮増殖因子を含む、低血清増殖添加物(LSGS)を追加した基礎培地200(カスケード・バイオロジクス)をHUVECのために使用した。8-12の継代の細胞を接着試験のために用いた。C.E van der Schoot博士(アムステルダムの大学、アムステルダム、オランダ)により提供されたヒト骨髄内皮細胞系統、HBMEC-60は、両種指向性ヘルパー-フリーレトロウイルスpLXSN16 E6/E7を用いて(32)、元は成人ヒト骨髄から単離されたHBMECの不死化により開発した。HBMEC-60細胞は、その正常なフェノタイプおよび接着特性、特に造血前駆細胞に結合するその能力を維持することが示された(32)。20%FBSおよび、ヒドロコルチソン、ヒト繊維芽細胞増殖因子、ヘパリンおよびヒト表皮増殖因子を含むLSGSを追加した基礎培地200(カスケード・バイオロジクス)をHBMEC-60のために使用した。細胞を加湿したインキュベーター中(5%CO2)で37℃で単層培養物状態で維持した。
本実施例は、モノクローナル抗体が、エキソビボ様式で、転移および転移性腫瘍形成の重要な段階を遮断できることを示す。かかる試験を行うために、灌流された豚硬膜を既に記載されているように(33-34)、接着試験で用いた。簡単には、ミッソーリ大学承認の動物ケアプロトコル(the University of Missouri approved animal care protocol)に従い動物を屠殺した後30分以内の成熟した雌のユカタン・ミニチュアブタ(チャールズ・リバー、ME)から回収した一半球に対応する硬膜を切開し、シルガード(Sylgard)-コートした100mm皿に広げた。正中硬膜動脈の主要な分岐にカニューレを挿入し、硬膜血管を、まず1.0mg/mlのブタ血清アルブミンを追加したクレブス生理塩を用いて20分間15μl/分で灌流し、次いで血管標識溶液(10%FBSと1.0mg/mlブタアルブミンを追加したRPMI-1640中0.3μg/mlのアクリジンオレンジ溶液)でさらに40分間灌流した。注入前に、癌細胞を5分間、RPMI-1640培地中3μg/mlのアクリジンオレンジ溶液で前-標識し、3回濯ぎ、プラスチックから分離し、ピペットして単一細胞懸濁液を得、20μmのナイロンメッシュで濾過して細胞クランプを除去し、5・104細胞/mlに調整した。癌細胞の硬膜微細血管との相互作用をモニターし、75ワットのキセノンランプと高感度のCCDビデオカメラ(COHU、サンディエゴ、CA)を備えたLaborlux8顕微鏡(Leitz Wetzlar, ドイツ)に基づく蛍光ビデオ顕微鏡システムを用いて、1秒当たり30フレームでビデオ記録した。続くフレーム-バイ-フレーム分析のために、記録されたアナログビデオ画像をメディア・コンバーターDVMC-DA2(ソニー、日本)およびAdove Premier 6ソフトウェア(Adobeシステムズ、San Jose, CA)を用いてデジタル化した。
かかる試験からの結果を図2Cに示すが、この結果は、JAA-F11が、転移性腫瘍の形成における重要な段階であるブタの硬膜上でのヒト乳癌細胞ローリングを遮断することを示す。
本実施例は、間接細胞ELISA(Indirect Cellular ELISA)を用いるJAA-F11での、腫瘍細胞系統におけるTF-Agの検出を示す。かかる試験を行うために、5つのマウス癌細胞系統を試験した。4T1(ATCC番号:CRL-2539)およびJC(ATCC番号:CRL-2116)は共にBALB/c株乳腺癌由来である。4T1細胞系統は、ステージIVのヒト乳癌のための動物モデルである(35-37)。BALB/cマウスに注入した時、4T1は、一次腫瘍がインサイチュで増殖している間に、肺、肝臓、リンパ節および脳に転移し得る高転移性の腫瘍を自発的に生じる(35-37)。JCも、BALB/cマウスで腫瘍を生じ得る (38)。骨髄腫(ATCC番号:CRL-1580)はJAA-F11ハイブリドーマを作製するための融合パートナーであり(21)、TG-Ag-ネガティブ対照細胞系統として用いられた。LL(ATCC番号:CRL-1642)はこれもマウスからのルイス肺腺癌細胞系統である(39-40)。RIF細胞系統は照射誘導性線維肉腫である。LLのための培養培地〔4mMのL-グルタミンと1.5g/Lの二炭酸ナトリウムと4.5g/Lのグルコース(90%)+10%FBSを含むダルベッコの変更イーグル培地(DMED)〕を除き、他の4つの細胞系統は、2mMのL-グルタミンと1.5g/Lの二炭酸ナトリウム、4.5g/Lのグルコース、10mMのHEPESおよび1.0mMのピルビン酸ナトリウム(90%)+10%FBSを含むRPMI1640培地で増殖させた。
これらの結果は、mAb JAA-F11を、TF-Agを発現する癌細胞に選択的に結合させるために使用でき、乳癌細胞(4T1およびJC)および肺癌細胞(LL)細胞がTF-Agの非常に高いエクスプレッサーであることを示す。
本実施例は、細胞増殖におけるモノクローナル抗体JAA-F11の影響を示す。腫瘍細胞の増殖におけるJAA-F11の直接的な影響を調べるために、インビトロ増殖分析を行った(41-42)。4T1、ルイス肺、JC、RIFおよび骨髄腫細胞を実施例3に記載のごとく増殖させた。細胞を、72時間で増殖曲線の線形部分にある濃度で播いた。50μg/mlのJAA-F11 mAbを同時培養のために8ウェルの細胞の各々に添加した。Abを含まず培養培地のみの培養培地中の細胞をネガティブ対照として用いた。96ウェルプレート中での37℃、5%CO2での細胞増殖の68時間後、10μlのテトラゾリウム塩3-[4,5-ジメチルチアゾール-2-イル]-2,5-ジフェニル-テトラゾリウムブロマイド:チアゾイルブルー(MTT)を培養プレートの各ウェルに添加し、プレートを、72時間の全増殖時間のために4時間インキュベーターに戻した(41-42)。72時間のインキュベーション期間の終わりに、各ウェル中で生じた不溶解性のホルマザン生成物を、120μlの、イソプロパノール中5%の蟻酸を、強く混合しながら添加することにより溶解した。各ウェルのアブソーバンスを、ミクロプレートリーダーで570nmで、細胞の代謝活性の指標として測定した。
つまり、本実施例は、インビトロ腫瘍増殖を高めるTF-Agに対する他のAbsとは異なり、JAA-F11が、インビトロでの腫瘍細胞の増殖において統計学的に有意な阻害効果(約20%、p<0.01、これは細胞タイプにより異なる)を有することを示す。
本実施例では、モノクローナル抗体JAA-F11のインビボ抗-転移効果を示す。かかる試験を行うために4T1マウス乳癌モデルを用いた。4T1腫瘍細胞系統は、それをヒト乳癌のための適当な試験動物モデルとするいくつかの特徴を有する。まず、4T1腫瘍細胞はTF-Agポジティブであり、乳腺に容易に移植され、つまり、一次腫瘍がインサイチュで増殖し得、転移が容易に展開する。一次腫瘍は手術により除去でき、そのために、一次乳癌腫瘍が手術により除去され、かつ、転移性病巣が完全なままである臨床状況に匹敵するモデルにおいて、転移性疾患を研究することができる。
1. Springer, GF等、国立癌研究所のジャーナル(Journal of the National Cancer Institute)1975; 54(2):335-9.
2. Dippold, W等.環境衛生の展望(Environmental Health Perspectives)1990;88:255-7.
3. Maclean, G.D等.,癌生物学におけるセミナー(Seminar in Cancer Biology) 1991;2:433-439.
4. Glinsky, VV等, 癌研究(Cancer Research) 2001;61 : 4851-4857.
5. Glinsky, VV等., 癌研究2000;60: 2584-2588.
6. Springer, GF等., 生物化学のジャーナル(Journal of Biological Chemistry )1983;258:5702-5706.
7. Springer, GF等., 生物化学のジャーナル 1982;257(6):2744-6.
8. Springer, GF等., 腫瘍形成における臨床レビュー(Critical Reviews in Oncogenesis )1995;6:57-85.
10. Schirrmacher, V等,実験医薬のジャーナル(Journal of Experimental Medicine)1980;151(4):984-989.
11. Springer, GF., サイエンス(Science)1984;224:1198-1206.
12. Wolf, MF等., 腫瘍生物学(Tumor Biology)1988;9: 190-194.
13. Wolf, MF等., 癌研究1986;46:1779-1782.
14. Zanetti, M等., 国際免疫(International Immunology) 1993;5 : 113-119.
15. Springer, GF等., 癌バイオセラピー(Cancer Biotherapy)1994;9:7-15.
16. Avichezer, D等., 癌に関する国際ジャーナル(International Journal of Cancer)1997;72(1):119-27.
18. Choufani, G等., 癌(Cancer) 1999;86:2353-63.
19. Shigeoka, H等., 腫瘍生物学1999;20(3): 139-46.
20. Kishikawa, T等., 癌研究に関する日本のジャーナル(Japanese Journal of Cancer Research)1999;90:326-32.
21. Rittenhouse-Diakun, K等., ハイブリドーマ(Hybridoma)1998; 17(2): 165- 173.
22. Dessureault, S等., 乳癌研究および処置(Breast Cancer Research & Treatment) 1997;45(l):29-37.
23. Diakun, KR等., 免疫学的研究(Immunological Investigations)1987;16:151-163.
24. Franklin, WA. 癌1983;51:295-300.
26. O'Boyle, KP等, 癌研究(Cancer Research)1992;52(20):5663-7.
27. O'Boyle, KP等., ハイブリドーマ1996;15(6):401-8.
28. Holmberg, LA等., 骨髄移植(Bone Marrow Transplantation)2000;25(12): 1233-41.
29. Holmberg, LA等., 生物学的治療における専門的意見(Expert Opinion on Biological Therapy)2001; 1(5):881-91.
30. Longenecker, B等., 国立癌研究所のジャーナル1987;78: 489-496.
31. Gilewski, T等., アメリカ合衆国のサイエンスの国立アカデミーの会報(Proceedings of the National Academy of Sciences of the United States of America)2001;98(6):3270-5. 32. Rood, PML等., 臨床研究に関する欧州のジャーナル(European Journal of Clinical Investigation)2000;30:618-629.
34. Glinskii, OV等., 生理学に関するジャーナル(Journal of Physiology)(ロンドン) 2004;554:89-99.
35. Aslakson, CJ等, 癌研究1992;52: 1399-1405.
36. Pulaski, BA等., 癌研究1998;58:1486-1493.
37. Pulaski, BA等., 癌研究2000;60:2710-2715.
38. Chao, T-Y等., インビトロ細胞および発生生物学(In Vitro Cellular and Developmental Biology)1989;25(7):621-626.
39. Bertram, JS等., 癌レター(Cancer Letter)1980;l 1 :63-73.
40. Sharma, S等., 免疫学のジャーナル(Journal of Immunology)1999; 163:5020-5028.
41. O'Toole, SA等., 癌の検出および予防(Cancer Detection & Prevention) 2003;27(l):47-54.
42. Johnson, TA等.,癌に関する国際ジャーナル(International Journal of Cancer)2000;85(1):104-12.
Claims (14)
- 乳癌細胞、肺癌細胞、前立腺癌細胞および膵臓癌細胞から成る群から選択されるTF-Ag分子を発現している細胞の転移を個人において阻害するための組成物であって、
前記TF-Ag分子を発現している細胞の転移を阻害するのに十分な量のモノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)またはそのフラグメントを含む、組成物。 - 前記フラグメントがFab、Fab'、F(ab')2およびFvから成る群から選択される請求項1に記載の組成物。
- 前記モノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)がヒト化されたものである請求項1に記載の組成物。
- 前記モノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)が毒素および放射性アイソトープから成る群から選択される剤に結合されている請求項1に記載の組成物。
- 前記毒素がジフテリアA鎖およびリシンA鎖から成る群から選択される請求項4に記載の組成物。
- 前記放射性アイソトープがI 123 、I 125 、I 124 およびI 131 から成る群から選択される請求項4に記載の組成物。
- 化学療法剤と同時に、または連続的に投与される請求項1に記載のモノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)を含む組成物。
- 非経口、皮下、腹腔内、静脈内、リンパ内および肺内投与から成る群から選択される経路により投与される請求項1に記載のモノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)を含む組成物。
- 乳癌細胞、肺癌細胞、前立腺癌細胞および膵臓癌細胞から成る群から選択されるTF-Ag分子を発現している癌細胞の増殖を個人において阻害するための組成物であって、前記癌細胞の増殖を阻害するのに十分な量のモノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)またはそのフラグメントを含む組成物。
- 前記フラグメントがFab、Fab'、F(ab') 2 およびFvから成る群から選択される請求項9に記載の組成物。
- 前記モノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)がヒト化されたものである請求項9に記載の組成物。
- 前記モノクローナル抗体JAA-F11(ATCCカタログ番号CRL-2381)が毒素および放射性アイソトープから成る群から選択される剤に結合されている請求項9に記載の組成物。
- 前記毒素がジフテリアA鎖およびリシンA鎖から成る群から選択される請求項12に記載の組成物。
- 前記放射性アイソトープがI 123 、I 125 およびI 131 から成る群から選択される請求項12に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US59101104P | 2004-07-26 | 2004-07-26 | |
US60/591,011 | 2004-07-26 | ||
PCT/US2005/026317 WO2006012616A2 (en) | 2004-07-26 | 2005-07-26 | Therapeutic use of anti-tf-antigen antibody |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008507584A JP2008507584A (ja) | 2008-03-13 |
JP4904266B2 true JP4904266B2 (ja) | 2012-03-28 |
Family
ID=35786767
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007523692A Expired - Fee Related JP4904266B2 (ja) | 2004-07-26 | 2005-07-26 | 抗−tf−抗原抗体の治療的使用 |
Country Status (5)
Country | Link |
---|---|
US (2) | US7374755B2 (ja) |
EP (1) | EP1789027B1 (ja) |
JP (1) | JP4904266B2 (ja) |
CA (1) | CA2582252C (ja) |
WO (1) | WO2006012616A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014068719A (ja) * | 2012-09-28 | 2014-04-21 | Mitsubishi Electric Corp | 遠心分離装置 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2662226C (en) | 2006-09-10 | 2020-08-04 | Glycotope Gmbh | Fully human high yield production system for improved antibodies and proteins |
RS53996B1 (en) * | 2006-11-10 | 2015-10-30 | Glycotope Gmbh | COMPOSITIONS CONTAINING CORE-1 POSITIVE MICRO-ORGANISM AND THEIR APPLICATION FOR TREATMENT OR TUMOR PROPHYLAXIS |
EP1920782A1 (en) * | 2006-11-10 | 2008-05-14 | Glycotope Gmbh | Carboyhdrate specific cellular immunity inducing microorganisms and fractions thereof |
US7942742B2 (en) * | 2006-11-15 | 2011-05-17 | Cfph, Llc | Accessing identification information to verify a gaming device is in communications with a server |
EP2347769A1 (en) * | 2010-01-20 | 2011-07-27 | Glycotope GmbH | Cancer stem cell markers and uses thereof |
US9700610B2 (en) | 2011-08-22 | 2017-07-11 | Glycotope Gmbh | Microorganisms carrying a tumor antigen |
JP6740135B2 (ja) | 2014-04-18 | 2020-08-12 | ザ リサーチ ファウンデイション フォー ザ ステイト ユニバーシティー オブ ニューヨーク | ヒト化抗−tf−抗原抗体 |
US10023651B2 (en) | 2014-04-18 | 2018-07-17 | The Research Foundation For The State University Of New York | Humanized anti-TF-antigen antibodies |
CN109803670A (zh) | 2016-08-09 | 2019-05-24 | 曼达迈德股份有限公司 | 用于预防和治疗心脏损伤的方法和组合物 |
CA3100608A1 (en) | 2018-05-18 | 2019-11-21 | Daiichi Sankyo Co., Ltd. | Anti-muc1 antibody-drug conjugate |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4331647A (en) * | 1980-03-03 | 1982-05-25 | Goldenberg Milton David | Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers |
US7229774B2 (en) * | 2001-08-02 | 2007-06-12 | Regents Of The University Of Michigan | Expression profile of prostate cancer |
-
2005
- 2005-07-26 CA CA2582252A patent/CA2582252C/en active Active
- 2005-07-26 EP EP05804113.8A patent/EP1789027B1/en active Active
- 2005-07-26 JP JP2007523692A patent/JP4904266B2/ja not_active Expired - Fee Related
- 2005-07-26 US US11/190,165 patent/US7374755B2/en active Active
- 2005-07-26 WO PCT/US2005/026317 patent/WO2006012616A2/en active Application Filing
-
2008
- 2008-05-19 US US12/122,886 patent/US20080226561A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014068719A (ja) * | 2012-09-28 | 2014-04-21 | Mitsubishi Electric Corp | 遠心分離装置 |
Also Published As
Publication number | Publication date |
---|---|
WO2006012616A2 (en) | 2006-02-02 |
EP1789027A2 (en) | 2007-05-30 |
US7374755B2 (en) | 2008-05-20 |
US20080226561A1 (en) | 2008-09-18 |
CA2582252C (en) | 2014-08-26 |
US20060018913A1 (en) | 2006-01-26 |
EP1789027B1 (en) | 2013-09-04 |
EP1789027A4 (en) | 2009-09-23 |
CA2582252A1 (en) | 2006-02-02 |
WO2006012616A3 (en) | 2006-05-04 |
JP2008507584A (ja) | 2008-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4904266B2 (ja) | 抗−tf−抗原抗体の治療的使用 | |
AU725238B2 (en) | Antigen binding fragments that specifically detect cancer cells, nucleotides encoding the fragments, and use thereof for the prophylaxis and detection of cancers | |
US7183384B2 (en) | Monoclonal antibody 7H11 reactive with human cancer | |
JP2000511421A5 (ja) | ||
JPH05504330A (ja) | ヒトのがん腫と反応する新しい抗体 | |
EP2876114A1 (en) | Antibodies against CCR9 and applications thereof | |
EA030182B1 (ru) | Антитела, специфические для кадгерина-17 | |
CN102781964A (zh) | 抗cdh3抗体及其用途 | |
WO1992007466A1 (en) | Synergistic therapy with combinations of anti-tumor antibodies and biologically active agents | |
CA2113578A1 (en) | Trifunctional compounds having specificity for multi-drug resistant cells | |
US7560095B2 (en) | Cancer specific monoclonal antibodies | |
JP2003520250A (ja) | 一部の癌の治療における抗フェリチンモノクローナル抗体の使用 | |
US6440733B1 (en) | Monoclonal antibodies recognizing antigens on the surface of endothelial cells of tumor vessel | |
JP2919961B2 (ja) | 扁平上皮癌の抗原分化のためのモノクローナル抗体および同抗体の使用法 | |
JP2003508525A (ja) | 抗腫瘍抗体、タンパク質、及びそれらの使用 | |
CA2255540C (en) | Antigen binding fragments that specifically detect cancer cells, nucleotides encoding the fragments, and use thereof for the prophylaxis and detection of cancers | |
AU650080B2 (en) | Synergistic therapy with combinations of anti-tumor antibodies and biologically active agents | |
US7115722B1 (en) | Antigen binding fragments that specifically detect cancer cells, nucleotides encoding the fragments, and use thereof for the prophylaxis and detection of cancers | |
JPH1030000A (ja) | 腫瘍血管内皮表面の抗原を認識するモノクローナル抗体 | |
JPH06505628A (ja) | in vivoで増殖する不死化細胞によるタンパク質の生産 | |
CN101663049A (zh) | 证明cd44表面表达的细胞的细胞毒性介导 | |
AU7243200A (en) | Antigen binding fragments that specifically detect cancer cells, nucleotides encoding the fragments, and use thereof for the prophylaxis and detection of cancers | |
NZ505305A (en) | Antigen binding fragments that inhibit an antibody comprising amino acid sequences of H and L chain V regions of a scFv from binding to the surface of a cancer cell | |
CA2158572A1 (en) | Monoclonal antibody 88bv59, subclones and method of making |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080724 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110511 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110811 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110907 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111114 |
|
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: 20111207 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120106 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4904266 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150113 Year of fee payment: 3 |
|
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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |