JP6883579B2 - 新規抗pd−1抗体 - Google Patents
新規抗pd−1抗体 Download PDFInfo
- Publication number
- JP6883579B2 JP6883579B2 JP2018526985A JP2018526985A JP6883579B2 JP 6883579 B2 JP6883579 B2 JP 6883579B2 JP 2018526985 A JP2018526985 A JP 2018526985A JP 2018526985 A JP2018526985 A JP 2018526985A JP 6883579 B2 JP6883579 B2 JP 6883579B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- seq
- cells
- antigen
- binding
- 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
- 230000027455 binding Effects 0.000 claims description 275
- 238000009739 binding Methods 0.000 claims description 275
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 148
- 210000004027 cell Anatomy 0.000 claims description 139
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 134
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims description 86
- 102000048362 human PDCD1 Human genes 0.000 claims description 72
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 71
- 206010028980 Neoplasm Diseases 0.000 claims description 54
- 230000000694 effects Effects 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 39
- 239000013598 vector Substances 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 27
- 230000014509 gene expression Effects 0.000 claims description 25
- 201000011510 cancer Diseases 0.000 claims description 22
- 108091033319 polynucleotide Proteins 0.000 claims description 22
- 102000040430 polynucleotide Human genes 0.000 claims description 22
- 239000002157 polynucleotide Substances 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 238000012360 testing method Methods 0.000 claims description 19
- 241000282693 Cercopithecidae Species 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 14
- 210000003289 regulatory T cell Anatomy 0.000 claims description 13
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 11
- 230000028993 immune response Effects 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 230000035755 proliferation Effects 0.000 claims description 11
- 239000012472 biological sample Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 9
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 claims description 9
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 9
- 238000000159 protein binding assay Methods 0.000 claims description 9
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 7
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 5
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 claims description 5
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims description 5
- 230000004073 interleukin-2 production Effects 0.000 claims description 5
- 230000003827 upregulation Effects 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 238000011824 transgenic rat model Methods 0.000 claims description 4
- 229940124060 PD-1 antagonist Drugs 0.000 claims description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims 1
- 239000000427 antigen Substances 0.000 description 196
- 108091007433 antigens Proteins 0.000 description 194
- 102000036639 antigens Human genes 0.000 description 194
- 239000012634 fragment Substances 0.000 description 166
- 108090000623 proteins and genes Proteins 0.000 description 39
- 150000007523 nucleic acids Chemical group 0.000 description 33
- 235000001014 amino acid Nutrition 0.000 description 26
- 125000003275 alpha amino acid group Chemical group 0.000 description 25
- 230000006870 function Effects 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 25
- 150000001413 amino acids Chemical class 0.000 description 24
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 21
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 21
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 21
- 210000004443 dendritic cell Anatomy 0.000 description 21
- 239000000872 buffer Substances 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 18
- 230000009261 transgenic effect Effects 0.000 description 18
- 239000000562 conjugate Substances 0.000 description 16
- 238000002965 ELISA Methods 0.000 description 15
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 239000012636 effector Substances 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 210000004408 hybridoma Anatomy 0.000 description 15
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 14
- 230000009227 antibody-mediated cytotoxicity Effects 0.000 description 14
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 14
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 108010002350 Interleukin-2 Proteins 0.000 description 13
- 102000000588 Interleukin-2 Human genes 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 241000283707 Capra Species 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 12
- 108090000695 Cytokines Proteins 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 229960002621 pembrolizumab Drugs 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000000735 allogeneic effect Effects 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000000539 dimer Substances 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 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 7
- 241000282412 Homo Species 0.000 description 7
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 7
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 7
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 7
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- -1 cytocaracin B Chemical compound 0.000 description 7
- 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 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 210000001616 monocyte Anatomy 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 238000012286 ELISA Assay Methods 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 230000006052 T cell proliferation Effects 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000012537 formulation buffer Substances 0.000 description 6
- 102000048776 human CD274 Human genes 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 210000003292 kidney cell Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 6
- 230000001613 neoplastic effect Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 5
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 5
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000009260 cross reactivity Effects 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 239000008176 lyophilized powder Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 238000010188 recombinant method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241001529453 unidentified herpesvirus Species 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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 4
- 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 4
- 108091008048 CMVpp65 Proteins 0.000 description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 4
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 4
- 229940045513 CTLA4 antagonist Drugs 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
- 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 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 4
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- 241000282567 Macaca fascicularis Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 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 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000282832 Camelidae Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 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 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000007910 cell fusion Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000000084 colloidal system Substances 0.000 description 3
- 238000012875 competitive assay Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000016396 cytokine production Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 229960000975 daunorubicin Drugs 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000003292 diminished effect Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229940090044 injection Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000006193 liquid solution Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000013074 reference sample Substances 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000012146 running buffer Substances 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 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
- 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
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 241000255925 Diptera Species 0.000 description 2
- 241000255601 Drosophila melanogaster Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 244000285963 Kluyveromyces fragilis Species 0.000 description 2
- 241001138401 Kluyveromyces lactis Species 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 2
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 2
- 241000607720 Serratia Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 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 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 238000012867 alanine scanning Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 2
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 2
- 230000003302 anti-idiotype Effects 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000008135 aqueous vehicle Substances 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 229930189065 blasticidin Natural products 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 208000013056 classic Hodgkin lymphoma Diseases 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229960003301 nivolumab Drugs 0.000 description 2
- 239000002687 nonaqueous vehicle Substances 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229960003171 plicamycin Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 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
- 239000003352 sequestering agent Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- 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 2
- 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 2
- 229960004528 vincristine Drugs 0.000 description 2
- 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 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- DYIOSHGVFJTOAR-JGWLITMVSA-N (2r,3r,4s,5r)-6-sulfanylhexane-1,2,3,4,5-pentol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CS DYIOSHGVFJTOAR-JGWLITMVSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- 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 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- 241000256118 Aedes aegypti Species 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241001203868 Autographa californica Species 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000255789 Bombyx mori Species 0.000 description 1
- 241000409811 Bombyx mori nucleopolyhedrovirus Species 0.000 description 1
- 206010006143 Brain stem glioma Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- LWFDUMPGOAKHKC-UHFFFAOYSA-N C1=CC=C2C=C(C(=O)C(C(O)=C3O)=O)C3=CC2=C1 Chemical compound C1=CC=C2C=C(C(=O)C(C(O)=C3O)=O)C3=CC2=C1 LWFDUMPGOAKHKC-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010060123 Conjugate Vaccines Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000701022 Cytomegalovirus Species 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
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- SDKQRNRRDYRQKY-UHFFFAOYSA-N Dioxacarb Chemical compound CNC(=O)OC1=CC=CC=C1C1OCCO1 SDKQRNRRDYRQKY-UHFFFAOYSA-N 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241001524679 Escherichia virus M13 Species 0.000 description 1
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 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 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 241000829111 Human polyomavirus 1 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 108091008028 Immune checkpoint receptors Proteins 0.000 description 1
- 102000037978 Immune checkpoint receptors Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 241000701460 JC polyomavirus Species 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000481961 Lachancea thermotolerans Species 0.000 description 1
- 241000235651 Lachancea waltii Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 101000611935 Mus musculus Programmed cell death protein 1 Proteins 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 240000007377 Petunia x hybrida Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 241001123650 Schwanniomyces occidentalis Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 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
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 240000002670 Tagetes lucida Species 0.000 description 1
- 235000003591 Tagetes lucida Nutrition 0.000 description 1
- 241000960387 Torque teno virus Species 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 241000235013 Yarrowia Species 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229960000686 benzalkonium 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
- 229960001950 benzethonium chloride Drugs 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
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000012054 celltiter-glo Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 230000009668 clonal growth Effects 0.000 description 1
- 238000010372 cloning stem cell Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229940047120 colony stimulating factors Drugs 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
- 230000009918 complex formation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940031670 conjugate vaccine Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229940013361 cresol Drugs 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 101150063657 ecd gene Proteins 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- 108010011035 endodeoxyribonuclease DpnI Proteins 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 210000002458 fetal heart Anatomy 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 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 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 239000008236 heating water Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229940041669 mercury Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 208000007525 plasmablastic lymphoma Diseases 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000004492 positive regulation of T cell proliferation Effects 0.000 description 1
- 230000016412 positive regulation of cytokine production Effects 0.000 description 1
- 208000017805 post-transplant lymphoproliferative disease Diseases 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 108010038379 sargramostim Proteins 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229960004249 sodium acetate Drugs 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection 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
- 239000013589 supplement Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000013706 tagetes lucida Nutrition 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- UDEJEOLNSNYQSX-UHFFFAOYSA-J tetrasodium;2,4,6,8-tetraoxido-1,3,5,7,2$l^{5},4$l^{5},6$l^{5},8$l^{5}-tetraoxatetraphosphocane 2,4,6,8-tetraoxide Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)O1 UDEJEOLNSNYQSX-UHFFFAOYSA-J 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
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(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]([C@@H](C)O)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](CCCNC(N)=N)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)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)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=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/74—Inducing cell proliferation
-
- 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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Plant Pathology (AREA)
- Endocrinology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
a)配列番号1、配列番号3、および/または配列番号5を含む重鎖可変領域;
b)配列番号13、配列番号15、および/または配列番号5を含む重鎖可変領域;
c)配列番号1、配列番号15、および/または配列番号5を含む重鎖可変領域;
d)配列番号21、配列番号23、および/または配列番号25を含む重鎖可変領域;ならびに
e)配列番号33、配列番号35、および/または配列番号37を含む重鎖可変領域
からなる群から選択される重鎖可変領域を含む。
a)配列番号7、配列番号9、および/または配列番号11を含む軽鎖可変領域;
b)配列番号7、配列番号17、および/または 配列番号11を含む軽鎖可変領域;
c)配列番号7、配列番号17、および/または 配列番号19を含む軽鎖可変領域;
d)配列番号27、配列番号29、および/または 配列番号31を含む軽鎖可変領域;
e)配列番号39、配列番号41、および/または 配列番号43を含む軽鎖可変領域;ならびに
f)配列番号7、配列番号17、および/または 配列番号65を含む軽鎖可変領域
からなる群から選択される軽鎖可変領域を含む。
a)配列番号1、配列番号3、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号9、および/もしくは配列番号11を含む軽鎖可変領域;
b)配列番号13、配列番号15、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号11を含む軽鎖可変領域;
c)配列番号1、配列番号15、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号19を含む軽鎖可変領域;
d)配列番号21、配列番号23、および/もしくは配列番号25を含む重鎖可変領域ならびに配列番号27、配列番号29、および/もしくは配列番号31を含む軽鎖可変領域;
e)配列番号33、配列番号35、および/もしくは配列番号37を含む重鎖可変領域;ならびに配列番号39、配列番号41、および/もしくは配列番号43を含む軽鎖可変領域;または
f)配列番号1、配列番号15および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号65を含む軽鎖可変領域
を含む。
a)配列番号45を含む重鎖可変領域;および配列番号47を含む軽鎖可変領域;
b)配列番号49を含む重鎖可変領域;および配列番号51を含む軽鎖可変領域;
c)配列番号53を含む重鎖可変領域;および配列番号55を含む軽鎖可変領域;
d)配列番号57を含む重鎖可変領域;および配列番号59を含む軽鎖可変領域;
e)配列番号61を含む重鎖可変領域;および配列番号63を含む軽鎖可変領域;または、
f)配列番号53を含む重鎖可変領域;および配列番号67を含む軽鎖可変領域
を含む。
a)CD4+T細胞においてIL-2の産生を誘導する活性;
b)CD4+T細胞においてIFNγの産生を誘導する活性;
c)CD4+T細胞の増殖を誘導する活性;および
d)制御性T細胞の抑制機能を無効にする活性
のうち少なくとも1つを提供する。
本願発明は、例えば、以下の項目を提供する。
(項目1)
配列番号1、3、5、13、15、21、23、25、33、35および37からなる群から選択される重鎖CDR配列を含む、単離された抗体またはその抗原結合性断片。
(項目2)
配列番号7、9、11、17、19、27、29、31、39、41、43および65からなる群から選択される軽鎖CDR配列を含む、項目1に記載の抗体またはその抗原結合性断片。
(項目3)
先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片であって、
a)配列番号1、配列番号3、および/または配列番号5を含む重鎖可変領域;
b)配列番号13、配列番号15、および/または配列番号5を含む重鎖可変領域;
c)配列番号1、配列番号15、および/または配列番号5を含む重鎖可変領域;
d)配列番号21、配列番号23、および/または配列番号25を含む重鎖可変領域;ならびにe)配列番号33、配列番号35、および/または配列番号37を含む重鎖可変領域
からなる群から選択される重鎖可変領域を含む抗体またはその抗原結合性断片。
(項目4)
先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片であって、
a)配列番号7、配列番号9、および/または配列番号11を含む軽鎖可変領域;
b)配列番号7、配列番号17、および/または配列番号11を含む軽鎖可変領域;
c)配列番号7、配列番号17、および/または配列番号19を含む軽鎖可変領域;
d)配列番号27、配列番号29、および/または配列番号31を含む軽鎖可変領域;
e)配列番号39、配列番号41、および/または配列番号43を含む軽鎖可変領域;ならびにf)配列番号7、配列番号17、および/または配列番号65を含む軽鎖可変領域
からなる群から選択される軽鎖可変領域を含む抗体またはその抗原結合性断片。
(項目5)
先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片であって、
a)配列番号1、配列番号3、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号9、および/もしくは配列番号11を含む軽鎖可変領域;
b)配列番号13、配列番号15、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号11を含む軽鎖可変領域;
c)配列番号1、配列番号15、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号19を含む軽鎖可変領域;
d)配列番号21、配列番号23、および/もしくは配列番号25を含む重鎖可変領域;ならびに配列番号27、配列番号29、および/もしくは配列番号31を含む軽鎖可変領域;または
e)配列番号33、配列番号35、および/もしくは配列番号37を含む重鎖可変領域;ならびに配列番号39、配列番号41、および/もしくは配列番号43を含む軽鎖可変領域;または
f)配列番号1、配列番号15、および/もしくは配列番号5を含む重鎖可変領域;ならびに配列番号7、配列番号17、および/もしくは配列番号65を含む軽鎖可変領域
を含む抗体またはその抗原結合性断片。
(項目6)
配列番号45、配列番号49、配列番号53、配列番号57および配列番号61からなる群から選択される重鎖可変領域を含む、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目7)
配列番号47、配列番号51、配列番号55、配列番号59、配列番号63および配列番号67からなる群から選択される軽鎖可変領域を含む、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目8)
先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片であって、
a)配列番号45を含む重鎖可変領域;および配列番号47を含む軽鎖可変領域;
b)配列番号49を含む重鎖可変領域;および配列番号51を含む軽鎖可変領域;
c)配列番号53を含む重鎖可変領域;および配列番号55を含む軽鎖可変領域;
d)配列番号57を含む重鎖可変領域;および配列番号59を含む軽鎖可変領域;
e)配列番号61を含む重鎖可変領域;および配列番号63を含む軽鎖可変領域;または
f)配列番号53を含む重鎖可変領域;および配列番号67を含む軽鎖可変領域
を含む抗体またはその抗原結合性断片。
(項目9)
プラズモン共鳴結合アッセイで測定した場合に10 -8 M以下のKd値でヒトPD-1に特異的に結合することができる、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目10)
100nM以下もしくは10nM以下のEC50でサルPD-1に結合し、かつ/またはマウスPD-1に結合しない、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目11)
100nM以下のIC50でヒトPD-1またはサルPD-1のPD-1リガンドへの結合を阻害することができる、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目12)
CD28またはCTLA4に実質的に結合しない、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目13)
ADCCもしくはCDCまたはその両者を媒介しない、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目14)
完全ヒトモノクローナル抗体である、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目15)
完全ヒトモノクローナル抗体がトランスジェニックラットにより産生される、項目14に記載の抗体またはその抗原結合性断片。
(項目16)
先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片と同じエピトープについて競合する、抗体またはその抗原結合性断片。
(項目17)
ヒトPD-1のPD-1リガンドへの結合を阻害することができ、それによって、以下の活性:a)CD4 + T細胞においてIL-2産生を誘導する活性;
b)CD4 + T細胞においてIFNγ産生を誘導する活性;
c)CD4 + T細胞の増殖を誘導する活性;および
d)制御性T細胞の抑制機能を無効にする活性
のうち少なくとも1つの活性を提供する、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目18)
ラクダ化シングルドメイン抗体、ダイアボディ、scFv、二量体scFv、BsFv、dsFv、(dsFv)2、dsFv-dsFv'、Fvフラグメント、Fab、Fab'、F(ab')2、dsディアボディ、ナノボディ、ドメイン抗体、または2価ドメイン抗体である、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目19)
イムノグロブリン定常領域をさらに含む、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目20)
コンジュゲートをさらに含む、先行する項目のいずれか1項に記載の抗体またはその抗原結合性断片。
(項目21)
項目1〜19のいずれか1項に記載の抗体またはその抗原結合性断片をコードする単離されたポリヌクレオチド。
(項目22)
項目21に記載の単離されたポリヌクレオチドを含むベクター。
(項目23)
項目22に記載のベクターを含む宿主細胞。
(項目24)
項目21に記載のポリヌクレオチドが発現される条件下で項目23に記載の宿主細胞を培養することを含む、項目1〜19のいずれか1項に記載の抗体またはその抗原結合性断片を発現させる方法。
(項目25)
項目1〜20のいずれか1項に記載の抗体またはその抗原結合性断片を含むキット。
(項目26)
個体においてPD-1に関連した状態を治療する方法であって、治療上有効量の項目1〜20のいずれか1項に記載の抗体またはその抗原結合性断片を前記個体に投与することを含む方法。
(項目27)
前記個体がPD-1拮抗薬に反応する可能性がある障害または状態を有すると同定された個体である、項目26に記載の方法。
(項目28)
前記個体が、その個体由来の試験生体試料においてPD-L1の存在またはPD-L1のレベルの上昇について陽性であると同定されている、項目27に記載の方法。
(項目29)
項目1〜20のいずれか1項に記載の抗体またはその抗原結合性断片および1つ以上の薬学的に許容される担体を含む医薬組成物。
(項目30)
治療上有効量の項目1〜20のいずれか1項に記載の抗体またはその抗原結合性断片を対象に投与することを含む、その対象における免疫反応の上方調節により効果が見込める状態を治療する方法。
(項目31)
対象がPD-L1の発現の上昇を示す、項目30に記載の方法。
(項目32)
免疫反応の上方調節により効果が見込める状態を治療するための医薬の製造における、項目1〜20のいずれか1項に記載の抗体または抗原結合性断片の使用。
(項目33)
前記状態ががんまたは慢性ウイルス感染症である、項目32に記載の使用。
(項目34)
前記エピトープがPD-1の以下のアミノ酸残基:V64、P83、D85、L128、A129、P130、K131、A132およびQ133のうち少なくとも1つを含む、項目16に記載の抗体または抗原結合性断片。
本開示の以下の説明は、単に本開示の様々な実施形態を説明することを意図されるだけである。故に、説明される特定の変更は本開示の範囲を限定するものと理解されないべきである。様々な同等物、変化、および改変は本開示の範囲から逸脱することなしに実施され得ることが当業者には明らかであるし、そうした同等な実施形態は本発明に含まれるものと理解される。本明細書に引用されるすべての引用物は出版物、特許および特許出願を含めてすべて引用によって本明細書に組み込まれる。
本明細書で使用される「抗体」という用語は、特異的な抗原に結合するあらゆるイムノグロブリン、モノクローナル抗体、ポリクローナル抗体、多重特異性抗体、または二重特異性(2価)抗体を含む。天然の完全な抗体は2本の重鎖と2本の軽鎖を含む。各重鎖は可変領域と第1、第2、および第3の定常領域からなり、各軽鎖は可変領域と定常領域からなる。哺乳類の重鎖はα、δ、ε、γおよびμに分類され、哺乳類の軽鎖はλまたはκに分類される。抗体は「Y」の形をしていて、Yの基部はジスルフィド結合で1つに結合した2本の重鎖の第2および第3の定常領域からなる。Yの各アームは単一軽鎖の可変領域および定常領域に結合した単一重鎖の可変領域および第1定常領域を含む。軽鎖と重鎖の可変領域は抗原結合を担う。両鎖の可変領域は一般的に相補性決定領域(CDR)と呼ばれる3個の超可変ループを含む(軽(L)鎖CDRはLCDR1、LCDR2、およびLCDR3を含み、重(H)鎖CDRは、HCDR1、HCDR2、HCDR3を含む)。本明細書に開示される抗体および抗原結合性断片のCDRの境界はKabat、Chothia、またはAl-Lazikani(Al-Lazikani, B., Chothia, C., Lesk, A. M., J. Mol. Biol., 273(4), 927 (1997);Chothia, C. et al., J Mol Biol. Dec 5;186(3):651-63 (1985); Chothia, C. and Lesk, A.M., J.Mol.Biol., 196,901 (1987); Chothia, C. et al., Nature. Dec 21-28;342(6252):877-83 (1989);Kabat E.A. et al., National Institutes of Health, Bethesda, Md. (1991))の慣例によって定義または同定されうる。3個のCDRは、CDRに比べてより高度に保存されており超可変ループを支える足場を形成するフレームワーク領域(FR)として公知の隣接したストレッチに挟まれている。重鎖と軽鎖の定常領域は抗原結合に関わらないが、様々なエフェクター機能を示す。抗体は重鎖の定常領域のアミノ酸配列に基づきクラスに分類される。抗体の主要な5つのクラスまたはアイソタイプは、α、δ、ε、γおよびμの重鎖の存在によりそれぞれ特徴づけられるIgA、IgD、IgE、IgGおよびIgMである。主要な抗体クラスのうちの数種類はIgG1(γ1重鎖)、IgG2(γ2重鎖)、IgG3(γ3重鎖)、IgG4(γ4重鎖)、IgA1(α1重鎖)またはIgA2(α2重鎖)などのサブクラスに分けられる。
一態様では、本開示は抗PD-1抗体およびその抗原結合性断片を提供する。PD-1はCD279とも呼ばれ、活性化T細胞によって発現される鍵となる免疫チェックポイント受容体であり、免疫抑制を媒介する受容体として知られる。PD-1リガンド1(PD-1 ligand 1)(PD-L1)は様々な腫瘍細胞、ストローマ細胞、またはその両方に発現する40 kDaの膜貫通型タンパク質であり、PD-1に結合する。PD-1とPD-L1の間の相互作用の阻害は、T細胞の反応を増強することができ、それにより抗がん活性を媒介する。
本開示は抗PD-1抗体およびその抗原結合性断片をコードする単離されたポリヌクレオチドを提供する。一実施形態では、単離されたポリヌクレオチドは、表1に提供されるCDR配列をコードする、表1に示された1個以上の核酸配列を含む。
本開示は抗PD-1抗体またはその抗原結合性断片を含むキットを提供する。一部の実施形態では、前記キットは生体試料中のPD-1の存在またはレベルを検出するのに役立つ。生体試料は細胞または組織を含んでもよい。
本開示はさらに、抗PD-1抗体またはその抗原結合性断片と1個以上の薬学的に許容される担体を含む医薬組成物を提供する。
1.3 抗体ハイブリドーマの作製
2.1 抗体ハイブリドーマ細胞のシーケンス:RNAはモノクローナルハイブリドーマ細胞からTrizol試薬を用いて単離された。PD-1抗体のVHおよびVLが以下のプロトコルに従って増幅された:手短に述べれば、RNAはまず以下に述べるように逆転写酵素を使用してcDNAに逆転写される。
反応系(20μl):
10×RT緩衝液 2.0μl
25×dNTPミックス (100 mM) 0.8μl
10×RTランダムプライマー/オリゴdT/特異的プライマー 2.0μl
MultiScribe(商標)逆転写酵素 1.0μl
RNaseインヒビター 1.0μl
RNA 2μg
ヌクレアーゼフリーH2O 20.0μlまで
3.1 フローサイトメトリー(FACS)で試験される細胞表面PD-1分子へのPD-1抗体の結合親和性:細胞表面PD-1への抗体結合親和性がFACS解析により実施された。ヒトPD-1を発現するCHO-S細胞が5x105細胞/mlの密度で96ウェルU字底プレート(BD)の中へ移された。試験される抗体は洗浄緩衝液(1XPBS/1%BSA)で1:2で段階希釈され、4℃で1時間細胞とともにインキュベートされた。2次抗体であるヤギ抗ヒトIgG Fc FITC(モルIgG当たり3.0モルFITC(Jackson Immunoresearch Lab))が加えられ、暗所にて4℃で1時間インキュベートされた。細胞は次に1回洗浄され、1XPBS/1%BSA中に再懸濁され、フローサイトメトリー(BD)で解析された。蛍光強度は、定量ビーズであるQuantum(商標) MESFキット(Bangs Laboratories, Inc.)に基づいて結合した分子/細胞比率に変換される。KDはグラフパッドプリズム5を使用して計算された。図2は完全ヒトPD-1抗体(すなわち1.7.3 hAb、1.49.9 hAb、1.103.11 hAb、1.139.15 hAb、および1.153.7 hAb)の、PD-1を発現するCHO細胞への結合を示す。ヒトPD-1に対する完全ヒト抗体はPD-1を遺伝子導入されたCHO細胞を染色するために使用され、完全ヒトPD-1抗体が約2nmol/LのEC50で特異的にPD-1に結合することをFACS解析が示す。
3.4.1 PD-1抗体の結合エピトープは、ProteOn XPR36(バイオ・ラッド)を使用したSPRアッセイにより基準抗体AおよびBに対してビン決定を行った。基準抗体AおよびBは、アミンカップリングを通じてGLCセンサーチップ(バイオ・ラッド)上に固定化された。ヒトPD-1溶液は抗体固定化流路上に流され、基準抗体に捕捉された。チップは次に90°回転され、ベースラインが安定になるまでランニング緩衝液により洗浄された。選択された抗体はセンサーチップ上に流された。
本明細書で提供される本発明の抗体1.103.11 hAbと公知のhPD-1抗体であるキイトルーダとの間のエピトープの違いを決定するために、hPD-1に関するアラニンスキャニング実験および抗体結合への効果の評価が1.103.11 hAb、キイトルーダおよび11.148.10(1.103.11 hAbのエピトープまたはキイトルーダのエピトープと重ならないエピトープに結合する対照hPD-1抗体)を使用して行われた。
Claims (25)
- 配列番号53を含む重鎖可変領域と配列番号67を含む軽鎖可変領域とを含む、単離された抗PD−1抗体。
- プラズモン共鳴結合アッセイで測定した場合に10-8M以下のKd値でヒトPD-1に特異的に結合することができる、請求項1に記載の抗体。
- 100nM以下もしくは10nM以下のEC50でサルPD-1に結合し、かつ/またはマウスPD-1に結合しない、請求項1または2に記載の抗体。
- 100nM以下のIC50でヒトPD-1またはサルPD-1のPD-1リガンドへの結合を阻害することができる、請求項1〜3のいずれか1項に記載の抗体。
- CD28またはCTLA4に実質的に結合しない、請求項1〜4のいずれか1項に記載の抗体。
- ADCCもしくはCDCまたはその両者を媒介しない、請求項1〜5のいずれか1項に記載の抗体。
- 完全ヒトモノクローナル抗体である、請求項1〜6のいずれか1項に記載の抗体。
- 完全ヒトモノクローナル抗体がトランスジェニックラットにより産生される、請求項7に記載の抗体。
- ヒトPD-1のPD-1リガンドへの結合を阻害することができ、それによって、以下の活性:a)CD4+T細胞においてIL-2産生を誘導する活性;
b)CD4+T細胞においてIFNγ産生を誘導する活性;
c)CD4+T細胞の増殖を誘導する活性;および
d)制御性T細胞の抑制機能を無効にする活性
のうち少なくとも1つの活性を提供する、請求項1〜8のいずれか1項に記載の抗体。 - イムノグロブリン定常領域をさらに含む、請求項1〜9のいずれか1項に記載の抗体。
- コンジュゲートをさらに含む、請求項1〜10のいずれか1項に記載の抗体。
- 請求項1〜11のいずれか1項に記載の抗体をコードする単離されたポリヌクレオチド。
- 請求項12に記載の単離されたポリヌクレオチドを含むベクター。
- 請求項13に記載のベクターを含む宿主細胞。
- 請求項12に記載のポリヌクレオチドが発現される条件下で請求項14に記載の宿主細胞を培養することを含む、請求項1〜10のいずれか1項に記載の抗体を発現させる方法。
- 請求項1〜11のいずれか1項に記載の抗体を含むキット。
- 個体においてPD-1に関連した状態を治療するための、請求項1〜11のいずれか1項に記載の抗体を含む組成物。
- 前記個体がPD-1拮抗薬に反応する可能性がある障害または状態を有すると同定された個体である、請求項17に記載の組成物。
- 前記個体が、その個体由来の試験生体試料においてPD-L1の存在またはPD-L1のレベルの上昇について陽性であると同定されている、請求項18に記載の組成物。
- 請求項1〜11のいずれか1項に記載の抗体および1つ以上の薬学的に許容される担体を含む医薬組成物。
- 請求項1〜11のいずれか1項に記載の抗体を含む、免疫反応の上方調節により効果が見込める対象における状態を治療するための組成物。
- 対象がPD-L1の発現の上昇を示す、請求項21に記載の組成物。
- 免疫反応の上方調節により効果が見込める状態を治療するための医薬の製造における、請求項1〜11のいずれか1項に記載の抗体の使用。
- 前記状態ががんまたは慢性ウイルス感染症である、請求項23に記載の使用。
- 前記完全ヒトモノクローナル抗体がIgG4抗体である、請求項7に記載の抗体。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CN2015/086594 WO2017024515A1 (en) | 2015-08-11 | 2015-08-11 | Novel anti-pd-1 antibodies |
CNPCT/CN2015/086594 | 2015-08-11 | ||
CNPCT/CN2016/071374 | 2016-01-19 | ||
CN2016071374 | 2016-01-19 | ||
PCT/CN2016/094624 WO2017025051A1 (en) | 2015-08-11 | 2016-08-11 | Novel anti-pd-1 antibodies |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020200034A Division JP2021036914A (ja) | 2015-08-11 | 2020-12-02 | 新規抗pd−1抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018527950A JP2018527950A (ja) | 2018-09-27 |
JP6883579B2 true JP6883579B2 (ja) | 2021-06-09 |
Family
ID=57982964
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018526985A Active JP6883579B2 (ja) | 2015-08-11 | 2016-08-11 | 新規抗pd−1抗体 |
JP2020200034A Withdrawn JP2021036914A (ja) | 2015-08-11 | 2020-12-02 | 新規抗pd−1抗体 |
JP2022131714A Pending JP2022161997A (ja) | 2015-08-11 | 2022-08-22 | 新規抗pd-1抗体 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020200034A Withdrawn JP2021036914A (ja) | 2015-08-11 | 2020-12-02 | 新規抗pd−1抗体 |
JP2022131714A Pending JP2022161997A (ja) | 2015-08-11 | 2022-08-22 | 新規抗pd-1抗体 |
Country Status (22)
Country | Link |
---|---|
US (3) | US11008391B2 (ja) |
EP (1) | EP3334763B1 (ja) |
JP (3) | JP6883579B2 (ja) |
KR (1) | KR102055396B1 (ja) |
AU (2) | AU2016305697B2 (ja) |
BR (1) | BR112018002824A2 (ja) |
CA (1) | CA2993276A1 (ja) |
CL (1) | CL2018000370A1 (ja) |
CO (1) | CO2018000992A2 (ja) |
EA (1) | EA201890468A1 (ja) |
EC (1) | ECSP18018842A (ja) |
IL (2) | IL293385A (ja) |
MA (1) | MA42626A (ja) |
MX (2) | MX2018001644A (ja) |
MY (1) | MY187739A (ja) |
PE (1) | PE20181018A1 (ja) |
PH (1) | PH12018500183A1 (ja) |
RU (2) | RU2020124273A (ja) |
SA (2) | SA518390903B1 (ja) |
SG (1) | SG10201914109VA (ja) |
UA (1) | UA124379C2 (ja) |
WO (1) | WO2017025051A1 (ja) |
Families Citing this family (98)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG10201913303XA (en) | 2015-07-13 | 2020-03-30 | Cytomx Therapeutics Inc | Anti-pd-1 antibodies, activatable anti-pd-1 antibodies, and methods of use thereof |
IL293385A (en) | 2015-08-11 | 2022-07-01 | Omniab Inc | New anti–pd–1 antibodies |
WO2017058859A1 (en) | 2015-09-29 | 2017-04-06 | Celgene Corporation | Pd-1 binding proteins and methods of use thereof |
EA201891165A1 (ru) | 2015-11-18 | 2018-11-30 | Мерк Шарп И Доум Корп. | Молекулы, связывающие pd1 и/или lag3 |
KR102531889B1 (ko) | 2016-06-20 | 2023-05-17 | 키맵 리미티드 | 항-pd-l1 및 il-2 사이토카인 |
US10751414B2 (en) | 2016-09-19 | 2020-08-25 | Celgene Corporation | Methods of treating psoriasis using PD-1 binding antibodies |
JP2019534859A (ja) | 2016-09-19 | 2019-12-05 | セルジーン コーポレイション | Pd−1結合タンパク質を使用して白斑を治療する方法 |
AU2016423559C1 (en) | 2016-09-21 | 2020-11-19 | Cstone Pharmaceuticals | The novel monoclonal antibodies to programmed death 1 (PD-1) |
US20190315865A1 (en) | 2016-10-28 | 2019-10-17 | Bristol-Myers Squibb Company | Methods of treating urothelial carcinoma using an anti-pd-1 antibody |
JP7039582B2 (ja) | 2016-11-03 | 2022-03-22 | ブリストル-マイヤーズ スクイブ カンパニー | 活性化可能な抗ctla-4抗体およびその使用 |
EP3601355A1 (en) | 2017-03-31 | 2020-02-05 | Bristol-Myers Squibb Company | Methods of treating tumor |
TWI788340B (zh) | 2017-04-07 | 2023-01-01 | 美商必治妥美雅史谷比公司 | 抗icos促效劑抗體及其用途 |
CN106939049B (zh) * | 2017-04-20 | 2019-10-01 | 苏州思坦维生物技术股份有限公司 | 拮抗抑制人pd-1抗原与其配体结合的单克隆抗体及其制备方法与应用 |
CN110678200B (zh) | 2017-05-30 | 2024-05-17 | 百时美施贵宝公司 | 包含抗lag-3抗体或抗lag-3抗体和抗pd-1或抗pd-l1抗体的组合物 |
EP4245375A3 (en) | 2017-05-30 | 2023-12-06 | Bristol-Myers Squibb Company | Compositions comprising a combination of an anti-lag-3 antibody, a pd-1 pathway inhibitor, and an immunotherapeutic agent |
HRP20231457T1 (hr) | 2017-05-30 | 2024-05-10 | Bristol-Myers Squibb Company | Liječenje lag-3-pozitivnih tumora |
WO2018223040A1 (en) | 2017-06-01 | 2018-12-06 | Bristol-Myers Squibb Company | Methods of treating a tumor using an anti-pd-1 antibody |
US10995149B2 (en) | 2017-06-05 | 2021-05-04 | Janssen Biotech, Inc. | Antibodies that specifically bind PD-1 and methods of use |
MX2020001328A (es) | 2017-08-03 | 2020-03-20 | Amgen Inc | Muteinas de interleucina 21 y metodos de tratamiento. |
KR20200064132A (ko) | 2017-10-15 | 2020-06-05 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
AU2018360790A1 (en) | 2017-11-06 | 2020-06-11 | Bristol-Myers Squibb Company | Methods of treating a tumor |
CN111727197A (zh) | 2018-01-12 | 2020-09-29 | 美国安进公司 | 抗pd-1抗体和治疗方法 |
KR20200120641A (ko) | 2018-01-15 | 2020-10-21 | 난징 레전드 바이오테크 씨오., 엘티디. | Pd-1에 대한 단일-도메인 항체 및 이의 변이체 |
KR20200109339A (ko) | 2018-01-16 | 2020-09-22 | 브리스톨-마이어스 스큅 컴퍼니 | Tim3에 대한 항체를 사용하여 암을 치료하는 방법 |
EP3743061A1 (en) | 2018-01-22 | 2020-12-02 | Pascal Biosciences Inc. | Cannabinoids and derivatives for promoting immunogenicity of tumor and infected cells |
CA3088542A1 (en) | 2018-01-22 | 2019-07-25 | Bristol-Myers Squibb Company | Compositions and methods of treating cancer |
AU2019237212A1 (en) * | 2018-03-22 | 2020-09-24 | Keires Ag | Antagonistic PD-1, PD-L1 and LAG-3 binding proteins |
TW202003565A (zh) | 2018-03-23 | 2020-01-16 | 美商必治妥美雅史谷比公司 | 抗mica及/或micb抗體及其用途 |
WO2019191676A1 (en) | 2018-03-30 | 2019-10-03 | Bristol-Myers Squibb Company | Methods of treating tumor |
JP2021520201A (ja) | 2018-04-04 | 2021-08-19 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗cd27抗体およびその使用 |
CN112368020B (zh) | 2018-05-07 | 2024-05-31 | 展马博联合股份有限公司 | 抗pd-1抗体和抗组织因子抗体-药物偶联物组合治疗癌症的方法 |
EP3826660A1 (en) | 2018-07-26 | 2021-06-02 | Bristol-Myers Squibb Company | Lag-3 combination therapy for the treatment of cancer |
WO2020057610A1 (en) * | 2018-09-20 | 2020-03-26 | Wuxi Biologics (Shanghai) Co., Ltd. | Novel bispecific anti-ctla-4/pd-1 polypeptide complexes |
CN112839962A (zh) | 2018-10-09 | 2021-05-25 | 百时美施贵宝公司 | 用于治疗癌症的抗mertk抗体 |
SG11202102864XA (en) | 2018-10-19 | 2021-05-28 | Bristol Myers Squibb Co | Combination therapy for melanoma |
JP2022505647A (ja) | 2018-10-23 | 2022-01-14 | ブリストル-マイヤーズ スクイブ カンパニー | 腫瘍の処置方法 |
PE20211284A1 (es) | 2018-11-16 | 2021-07-19 | Bristol Myers Squibb Co | Anticuerpos anti-nkg2a y usos de los mismos |
KR20210146349A (ko) | 2019-03-28 | 2021-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
KR20210146348A (ko) | 2019-03-28 | 2021-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
KR20220016156A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 요법에의 적합성을 위한 다종양 유전자 시그너쳐 |
WO2020243570A1 (en) | 2019-05-30 | 2020-12-03 | Bristol-Myers Squibb Company | Cell localization signature and combination therapy |
EP3976832A1 (en) | 2019-05-30 | 2022-04-06 | Bristol-Myers Squibb Company | Methods of identifying a subject suitable for an immuno-oncology (i-o) therapy |
CA3143680A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and anti-pd-1 or anti-pd-l1 antibody |
MA56533A (fr) | 2019-06-18 | 2022-04-27 | Janssen Sciences Ireland Unlimited Co | Combinaison de vaccins contre le virus de l'hépatite b (vhb) et d'anticorps anti-pd-1 |
KR20220030956A (ko) | 2019-07-05 | 2022-03-11 | 오노 야꾸힝 고교 가부시키가이샤 | Pd-1/cd3 이중 특이성 단백질에 의한 혈액암 치료 |
CN114144429B (zh) * | 2019-07-16 | 2023-10-13 | 上海药明生物技术有限公司 | 针对pd-1和lag-3的双特异性抗体 |
US20220332825A1 (en) | 2019-08-08 | 2022-10-20 | Ono Pharmaceutical Co., Ltd. | Bispecific protein |
US20220348653A1 (en) | 2019-09-22 | 2022-11-03 | Bristol-Myers Squibb Company | Quantitative Spatial Profiling for LAG-3 Antagonist Therapy |
MX2022003487A (es) | 2019-09-25 | 2022-04-25 | Bristol Myers Squibb Co | Biomarcador compuesto para terapia de cancer. |
JP2022553821A (ja) | 2019-11-05 | 2022-12-26 | ブリストル-マイヤーズ スクイブ カンパニー | M-タンパク質アッセイおよびその使用 |
WO2021092220A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
WO2021092221A1 (en) | 2019-11-06 | 2021-05-14 | Bristol-Myers Squibb Company | Methods of identifying a subject with a tumor suitable for a checkpoint inhibitor therapy |
AU2020380384A1 (en) | 2019-11-08 | 2022-05-26 | Bristol-Myers Squibb Company | LAG-3 antagonist therapy for melanoma |
WO2021097256A1 (en) | 2019-11-14 | 2021-05-20 | Cohbar, Inc. | Cxcr4 antagonist peptides |
AU2020407130A1 (en) | 2019-12-19 | 2022-06-16 | Bristol-Myers Squibb Company | Combinations of DGK inhibitors and checkpoint antagonists |
WO2021152548A1 (en) | 2020-01-30 | 2021-08-05 | Benitah Salvador Aznar | Combination therapy for treatment of cancer and cancer metastasis |
EP4100426A1 (en) | 2020-02-06 | 2022-12-14 | Bristol-Myers Squibb Company | Il-10 and uses thereof |
BR112022016720A2 (pt) | 2020-03-06 | 2022-11-16 | Ona Therapeutics S L | Anticorpos anti-cd36 e seu uso para tratamento de câncer |
MX2022011701A (es) | 2020-03-23 | 2022-10-07 | Bristol Myers Squibb Co | Anticuerpos anti-receptor de quimiocina 8 con motivo c-c (ccr8) para el tratamiento del cancer. |
KR20230058442A (ko) | 2020-08-28 | 2023-05-03 | 브리스톨-마이어스 스큅 컴퍼니 | 간세포성 암종에 대한 lag-3 길항제 요법 |
WO2022047412A1 (en) | 2020-08-31 | 2022-03-03 | Bristol-Myers Squibb Company | Cell localization signature and immunotherapy |
CN114316022A (zh) * | 2020-09-30 | 2022-04-12 | 正大天晴康方(上海)生物医药科技有限公司 | 结合pd-1抗体的肽及其应用 |
JP2023544410A (ja) | 2020-10-05 | 2023-10-23 | ブリストル-マイヤーズ スクイブ カンパニー | タンパク質を濃縮するための方法 |
JP2023548051A (ja) | 2020-10-23 | 2023-11-15 | ブリストル-マイヤーズ スクイブ カンパニー | 肺がんのためのlag-3アンタゴニスト療法 |
KR20230098279A (ko) | 2020-10-28 | 2023-07-03 | 이케나 온콜로지, 인코포레이티드 | Pdx 억제제 또는 독소루비신과 ahr 억제제의 조합 |
EP4247849A2 (en) | 2020-11-17 | 2023-09-27 | Seagen Inc. | Methods of treating cancer with a combination of tucatinib and an anti-pd-1/anti-pd-l1 antibody |
WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
JP2024503265A (ja) | 2020-12-28 | 2024-01-25 | ブリストル-マイヤーズ スクイブ カンパニー | 抗体組成物およびその使用の方法 |
MX2023007650A (es) | 2020-12-28 | 2023-09-11 | Bristol Myers Squibb Co | Metodos de tratamiento de tumores. |
BR112023015652A2 (pt) * | 2021-02-04 | 2023-10-17 | Genuv Inc | Anticorpo ou fragmento de ligação a antígeno do mesmo que se liga a um epítopo de uma proteína de morte celular programada 1 (pd-1); molécula de ácido nucleico; vetor de clonagem ou de expressão; célula hospedeira; método para produzir o anticorpo ou fragmento de ligação a antígeno do mesmo; animal transgênico; molécula de ligação a antígeno multiespecífico, imunoconjugado, receptor de antígeno quimérico, receptor de célula t modificado ou vírus oncolítico; composição farmacêutica para prevenir ou tratar uma afecção associada a pd-1; método para prevenir ou tratar tumores, doenças autoimunes de câncer, doenças autoimunes, doenças neurológicas, doenças neurodegenerativas ou doenças infecciosas; composição farmacêutica para aumentar uma resposta imunológica em um indivíduo que tem câncer; e hibridoma |
JP2024514245A (ja) | 2021-03-29 | 2024-03-29 | ジュノー セラピューティクス インコーポレイテッド | チェックポイント阻害剤療法とcar t細胞療法との組合せを用いた投薬および処置のための方法 |
EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
AU2022312698A1 (en) | 2021-07-13 | 2024-01-25 | BioNTech SE | Multispecific binding agents against cd40 and cd137 in combination therapy for cancer |
CN118488964A (zh) | 2021-07-30 | 2024-08-13 | Ona疗法有限公司 | 抗cd36抗体及其治疗癌症的用途 |
IL311771A (en) | 2021-10-06 | 2024-05-01 | BioNTech SE | Multispecific binding agents against PD-L1 and CD137 in combination |
IL309227A (en) | 2021-10-29 | 2024-02-01 | Bristol Myers Squibb Co | LAG-3 antagonist therapy for hematological cancer |
WO2023083439A1 (en) | 2021-11-09 | 2023-05-19 | BioNTech SE | Tlr7 agonist and combinations for cancer treatment |
IL314050A (en) | 2022-01-26 | 2024-09-01 | Bristol Myers Squibb Co | Combined treatment method for hepatocellular carcinoma |
AU2023226078A1 (en) | 2022-02-25 | 2024-08-22 | Bristol-Myers Squibb Company | Combination therapy for colorectal carcinoma. |
WO2023168404A1 (en) | 2022-03-04 | 2023-09-07 | Bristol-Myers Squibb Company | Methods of treating a tumor |
WO2023170606A1 (en) | 2022-03-08 | 2023-09-14 | Alentis Therapeutics Ag | Use of anti-claudin-1 antibodies to increase t cell availability |
WO2023178329A1 (en) | 2022-03-18 | 2023-09-21 | Bristol-Myers Squibb Company | Methods of isolating polypeptides |
WO2023196987A1 (en) | 2022-04-07 | 2023-10-12 | Bristol-Myers Squibb Company | Methods of treating tumor |
US20230326022A1 (en) | 2022-04-08 | 2023-10-12 | Bristol-Myers Squibb Company | Machine Learning Identification, Classification, and Quantification of Tertiary Lymphoid Structures |
WO2023201267A1 (en) | 2022-04-13 | 2023-10-19 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
WO2023205754A2 (en) * | 2022-04-20 | 2023-10-26 | University Of Utah Research Foundation | Antibodies specific to pd-1 and methods of use |
WO2023218046A1 (en) | 2022-05-12 | 2023-11-16 | Genmab A/S | Binding agents capable of binding to cd27 in combination therapy |
WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
EP4310197A1 (en) | 2022-07-21 | 2024-01-24 | Fundación para la Investigación Biomédica del Hospital Universitario Puerta de Hierro Majadahonda | Method for identifying lung cancer patients for a combination treatment of immuno- and chemotherapy |
WO2024069009A1 (en) | 2022-09-30 | 2024-04-04 | Alentis Therapeutics Ag | Treatment of drug-resistant hepatocellular carcinoma |
WO2024115725A1 (en) | 2022-12-01 | 2024-06-06 | BioNTech SE | Multispecific antibody against cd40 and cd137 in combination therapy with anti-pd1 ab and chemotherapy |
WO2024116140A1 (en) | 2022-12-01 | 2024-06-06 | Medimmune Limited | Combination therapy for treatment of cancer comprising anti-pd-l1 and anti-cd73 antibodies |
WO2024137776A1 (en) | 2022-12-21 | 2024-06-27 | Bristol-Myers Squibb Company | Combination therapy for lung cancer |
WO2024137442A1 (en) | 2022-12-21 | 2024-06-27 | Gilead Sciences, Inc. | Combination therapy for treating cancer |
CN116077645A (zh) * | 2022-12-28 | 2023-05-09 | 广州誉衡生物科技有限公司 | 抗-pd-1抗体及其在制备治疗非小细胞肺癌患者的药物中的用途 |
WO2024150177A1 (en) | 2023-01-11 | 2024-07-18 | Advesya | Treatment methods for solid tumors |
US20240294651A1 (en) | 2023-01-30 | 2024-09-05 | Kymab Limited | Antibodies |
Family Cites Families (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4879231A (en) | 1984-10-30 | 1989-11-07 | Phillips Petroleum Company | Transformation of yeasts of the genus pichia |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
GB8610600D0 (en) | 1986-04-30 | 1986-06-04 | Novo Industri As | Transformation of trichoderma |
WO1990003430A1 (en) | 1988-09-23 | 1990-04-05 | Cetus Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
EP0402226A1 (en) | 1989-06-06 | 1990-12-12 | Institut National De La Recherche Agronomique | Transformation vectors for yeast yarrowia |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
EP1621554B2 (en) | 1992-08-21 | 2012-08-29 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
US6838254B1 (en) | 1993-04-29 | 2005-01-04 | Conopco, Inc. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
EP1210428B1 (en) | 1999-08-23 | 2015-03-18 | Dana-Farber Cancer Institute, Inc. | Pd-1, a receptor for b7-4, and uses therefor |
AU2003281200A1 (en) | 2002-07-03 | 2004-01-23 | Tasuku Honjo | Immunopotentiating compositions |
CA2508660C (en) * | 2002-12-23 | 2013-08-20 | Wyeth | Antibodies against pd-1 and uses therefor |
GB0400440D0 (en) | 2004-01-09 | 2004-02-11 | Isis Innovation | Receptor modulators |
US7892540B2 (en) | 2004-10-06 | 2011-02-22 | Mayo Foundation For Medical Education And Research | B7-H1 and methods of diagnosis, prognosis, and treatment of cancer |
NZ563193A (en) | 2005-05-09 | 2010-05-28 | Ono Pharmaceutical Co | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
US8652465B2 (en) | 2005-06-08 | 2014-02-18 | Emory University | Methods and compositions for the treatment of persistent infections |
SI1907424T1 (sl) | 2005-07-01 | 2015-12-31 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska protitelesa proti programiranem smrtnem ligandu 1 (PD-L1) |
GB0614093D0 (en) | 2006-07-14 | 2006-08-23 | Bae Systems Plc | Deployable antenna system |
CL2007002225A1 (es) | 2006-08-03 | 2008-04-18 | Astrazeneca Ab | Agente de union especifico para un receptor del factor de crecimiento derivado de plaquetas (pdgfr-alfa); molecula de acido nucleico que lo codifica; vector y celula huesped que la comprenden; conjugado que comprende al agente; y uso del agente de un |
US8907065B2 (en) | 2006-12-15 | 2014-12-09 | Ablynx N.V. | Polypeptides that modulate the interaction between cells of the immune system |
LT2602323T (lt) | 2007-06-01 | 2018-04-10 | Open Monoclonal Technology, Inc. | Kompozicijos ir būdai endogeninių imunoglobulinų genams slopinti ir transgeniniams žmogaus idiotipo antikūnams gaminti |
ES2437327T3 (es) | 2007-06-18 | 2014-01-10 | Merck Sharp & Dohme B.V. | Anticuerpos para el receptor PD-1 humano de muerte programada |
JP5945096B2 (ja) * | 2008-07-04 | 2016-07-05 | 小野薬品工業株式会社 | 抗ヒトpd−1抗体の癌に対する治療効果を最適化するための判定マーカーの使用 |
AU2009319701B2 (en) | 2008-11-28 | 2014-10-09 | Dana-Farber Cancer Institute, Inc. | Methods for the treatment of infections and tumors |
CN114835812A (zh) | 2008-12-09 | 2022-08-02 | 霍夫曼-拉罗奇有限公司 | 抗-pd-l1抗体及它们用于增强t细胞功能的用途 |
CN101526890B (zh) | 2009-03-30 | 2011-01-05 | 昆山龙腾光电有限公司 | 显示拼接墙的显示单元的位置映射方法和装置 |
CN101763842B (zh) | 2009-11-13 | 2012-07-11 | 广东威创视讯科技股份有限公司 | 拼接墙墙体的配置系统及其建立显示单元的位置映射方法 |
CA2816225A1 (en) * | 2010-10-26 | 2012-05-03 | Technion Research & Development Foundation Ltd. | Antibodies which bind soluble t-cell receptor ligands |
RS57324B1 (sr) | 2011-04-20 | 2018-08-31 | Medimmune Llc | Antitela i drugi molekuli koji vezuju b7-h1 i pd-1 |
CA2852474A1 (en) * | 2011-10-18 | 2013-04-25 | Emory University | Antibodies directed against influenza |
JP2015135534A (ja) | 2012-05-09 | 2015-07-27 | パナソニック株式会社 | マルチ画面表示装置およびマルチ画面表示システム |
SG11201407190TA (en) | 2012-05-15 | 2014-12-30 | Bristol Myers Squibb Co | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
JPWO2013180200A1 (ja) * | 2012-05-30 | 2016-01-21 | 中外製薬株式会社 | 標的組織特異的抗原結合分子 |
CN102737616B (zh) | 2012-06-28 | 2015-07-08 | 广东威创视讯科技股份有限公司 | 大屏幕拼接墙单元位置自动识别方法及装置 |
CN103242448B (zh) | 2013-05-27 | 2015-01-14 | 郑州大学 | 一种全人源化抗pd-1单克隆抗体及其制备方法和应用 |
JP6563906B2 (ja) * | 2013-05-31 | 2019-08-21 | ソレント・セラピューティクス・インコーポレイテッドSorrento Therapeutics, Inc. | Pd−1に結合する抗原結合蛋白質 |
CN104250302B (zh) | 2013-06-26 | 2017-11-14 | 上海君实生物医药科技股份有限公司 | 抗pd‑1抗体及其应用 |
CN103701643B (zh) | 2013-12-23 | 2017-06-13 | 广东威创视讯科技股份有限公司 | 获取拼墙系统配置的方法、装置及拼墙系统 |
TWI681969B (zh) * | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
WO2015134605A1 (en) | 2014-03-05 | 2015-09-11 | Bristol-Myers Squibb Company | Treatment of renal cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
CN106714839A (zh) | 2014-05-15 | 2017-05-24 | 百时美施贵宝公司 | 使用抗pd‑1抗体和另一种抗癌剂的组合治疗肺癌 |
SG11201700207WA (en) | 2014-07-11 | 2017-02-27 | Genentech Inc | Anti-pd-l1 antibodies and diagnostic uses thereof |
RU2726996C1 (ru) | 2014-12-16 | 2020-07-17 | Бристол-Маерс Сквибб Компани | Применение ингибиторов иммунных контрольных точек при новообразованиях центральной нервной системы |
CN104479020B (zh) | 2014-12-26 | 2019-08-02 | 上海复宏汉霖生物技术股份有限公司 | 一种抗pd-1人源抗体 |
CN112263677A (zh) | 2015-02-26 | 2021-01-26 | 默克专利股份公司 | 用于治疗癌症的pd-1/pd-l1抑制剂 |
EP3265825A4 (en) | 2015-03-06 | 2018-08-08 | Dana-Farber Cancer Institute, Inc. | Pd-l2 biomarkers predictive of pd-1 pathway inhibitor responses in esophagogastric cancers |
ES2813580T3 (es) | 2015-04-17 | 2021-03-24 | Bristol Myers Squibb Co | Composiciones que comprenden una combinación de ipilimumab y nivolumab |
WO2016176503A1 (en) | 2015-04-28 | 2016-11-03 | Bristol-Myers Squibb Company | Treatment of pd-l1-negative melanoma using an anti-pd-1 antibody and an anti-ctla-4 antibody |
EP3288980B1 (en) | 2015-04-28 | 2021-03-10 | Bristol-Myers Squibb Company | Treatment of pd-l1-positive melanoma using an anti-pd-1 antibody |
WO2016191751A1 (en) | 2015-05-28 | 2016-12-01 | Bristol-Myers Squibb Company | Treatment of pd-l1 positive lung cancer using an anti-pd-1 antibody |
US11078278B2 (en) | 2015-05-29 | 2021-08-03 | Bristol-Myers Squibb Company | Treatment of renal cell carcinoma |
SI3322731T1 (sl) | 2015-07-14 | 2021-03-31 | Bristol-Myers Squibb Company | Postopek za zdravljenje raka z uporabo imunskega inhibitorja kontrolne točke; protitelo ki veže programiran receptor smrti (PD-1) ali programiran smrtni ligand 1 (PD-L1) |
EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
IL293385A (en) | 2015-08-11 | 2022-07-01 | Omniab Inc | New anti–pd–1 antibodies |
KR20180053752A (ko) | 2015-10-02 | 2018-05-23 | 심포젠 에이/에스 | 항-pd-1 항체 및 조성물 |
CN105336289A (zh) | 2015-10-30 | 2016-02-17 | 京东方科技集团股份有限公司 | 一种拼接控制方法、装置以及拼接屏系统 |
CN205017477U (zh) | 2015-10-30 | 2016-02-03 | 京东方科技集团股份有限公司 | 一种拼接控制装置以及拼接屏系统 |
CN106699889A (zh) | 2015-11-18 | 2017-05-24 | 礼进生物医药科技(上海)有限公司 | 抗pd-1抗体及其治疗用途 |
US20210206854A1 (en) | 2016-01-27 | 2021-07-08 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
WO2017176925A1 (en) | 2016-04-05 | 2017-10-12 | Bristol-Myers Squibb Company | Cytokine profiling analysis for predicting prognosis of a patient in need of an anti-cancer treatment |
PT3463457T (pt) | 2016-06-02 | 2023-09-07 | Bristol Myers Squibb Co | Bloqueio de pd-1 com nivolumab em linfoma de hodgkin refratário |
WO2017210637A1 (en) | 2016-06-03 | 2017-12-07 | Bristol-Myers Squibb Company | Use of anti-pd-1 antibody in the treatment of patients with colorectal cancer |
US20200325226A1 (en) | 2016-06-03 | 2020-10-15 | Bristol-Myers Squibb Company | Anti-pd-1 antibody for use in a method of treating a tumor |
AU2016423559C1 (en) | 2016-09-21 | 2020-11-19 | Cstone Pharmaceuticals | The novel monoclonal antibodies to programmed death 1 (PD-1) |
US20190315865A1 (en) | 2016-10-28 | 2019-10-17 | Bristol-Myers Squibb Company | Methods of treating urothelial carcinoma using an anti-pd-1 antibody |
CN110214153B (zh) | 2016-11-18 | 2024-03-29 | 法国施维雅药厂 | 抗pd-1抗体及组合物 |
WO2018132287A1 (en) | 2017-01-11 | 2018-07-19 | Dana-Farber Cancer Institute, Inc. | Pbrm1 biomarkers predictive of anti-immune checkpoint response |
KR102628557B1 (ko) | 2017-02-21 | 2024-01-29 | 리제너론 파아마슈티컬스, 인크. | 폐암의 치료를 위한 항-pd-1 항체 |
EP3601355A1 (en) | 2017-03-31 | 2020-02-05 | Bristol-Myers Squibb Company | Methods of treating tumor |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
WO2018223040A1 (en) | 2017-06-01 | 2018-12-06 | Bristol-Myers Squibb Company | Methods of treating a tumor using an anti-pd-1 antibody |
EP3658914A1 (en) | 2017-07-28 | 2020-06-03 | Bristol-Myers Squibb Company | Predictive peripheral blood biomarker for checkpoint inhibitors |
CN109575140B (zh) | 2017-09-29 | 2021-02-23 | 北京比洋生物技术有限公司 | 靶向pd-1或pd-l1且靶向vegf家族的双靶向融合蛋白及其用途 |
KR20200064132A (ko) | 2017-10-15 | 2020-06-05 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
CN109721657B (zh) | 2017-10-27 | 2021-11-02 | 北京比洋生物技术有限公司 | 阻断pd-1/pd-l1信号传导途径且活化t细胞的融合蛋白及其用途 |
-
2016
- 2016-08-11 IL IL293385A patent/IL293385A/en unknown
- 2016-08-11 EP EP16834675.7A patent/EP3334763B1/en active Active
- 2016-08-11 EA EA201890468A patent/EA201890468A1/ru unknown
- 2016-08-11 SG SG10201914109VA patent/SG10201914109VA/en unknown
- 2016-08-11 IL IL257062A patent/IL257062B/en unknown
- 2016-08-11 UA UAA201802340A patent/UA124379C2/uk unknown
- 2016-08-11 MX MX2018001644A patent/MX2018001644A/es unknown
- 2016-08-11 MA MA042626A patent/MA42626A/fr unknown
- 2016-08-11 CA CA2993276A patent/CA2993276A1/en active Pending
- 2016-08-11 PE PE2018000225A patent/PE20181018A1/es unknown
- 2016-08-11 RU RU2020124273A patent/RU2020124273A/ru unknown
- 2016-08-11 WO PCT/CN2016/094624 patent/WO2017025051A1/en active Application Filing
- 2016-08-11 MY MYPI2018700283A patent/MY187739A/en unknown
- 2016-08-11 US US15/751,236 patent/US11008391B2/en active Active
- 2016-08-11 RU RU2018108048A patent/RU2729830C2/ru active
- 2016-08-11 BR BR112018002824A patent/BR112018002824A2/pt active Search and Examination
- 2016-08-11 AU AU2016305697A patent/AU2016305697B2/en active Active
- 2016-08-11 JP JP2018526985A patent/JP6883579B2/ja active Active
- 2016-08-11 KR KR1020177036687A patent/KR102055396B1/ko active IP Right Grant
-
2018
- 2018-01-24 PH PH12018500183A patent/PH12018500183A1/en unknown
- 2018-01-30 CO CONC2018/0000992A patent/CO2018000992A2/es unknown
- 2018-02-08 MX MX2022006447A patent/MX2022006447A/es unknown
- 2018-02-09 CL CL2018000370A patent/CL2018000370A1/es unknown
- 2018-02-11 SA SA518390903A patent/SA518390903B1/ar unknown
- 2018-02-11 SA SA521422116A patent/SA521422116B1/ar unknown
- 2018-03-09 EC ECIEPI201818842A patent/ECSP18018842A/es unknown
-
2020
- 2020-12-02 JP JP2020200034A patent/JP2021036914A/ja not_active Withdrawn
-
2021
- 2021-04-26 US US17/239,866 patent/US11643465B2/en active Active
-
2022
- 2022-08-22 JP JP2022131714A patent/JP2022161997A/ja active Pending
-
2023
- 2023-02-16 AU AU2023200891A patent/AU2023200891A1/en active Pending
- 2023-03-20 US US18/186,793 patent/US20230348602A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6883579B2 (ja) | 新規抗pd−1抗体 | |
US20210269528A1 (en) | Novel anti-pd-l1 antibodies | |
US10696745B2 (en) | Anti-PD-L1 antibodies | |
WO2017024515A1 (en) | Novel anti-pd-1 antibodies | |
CN106432494B9 (zh) | 新型抗-pd-1抗体 | |
CN106432501B (zh) | 新型抗pd-l1抗体 | |
JP2019516394A (ja) | 新規抗pd−l1抗体 | |
JP7317858B2 (ja) | 単離された抗体またはその抗原結合断片、および腫瘍治療におけるその使用 | |
CN106243225B (zh) | 新型抗-pd-l1抗体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190802 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200625 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200714 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20201008 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201013 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20201013 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20201008 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201202 |
|
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: 20210413 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210510 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6883579 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |