CA2239448C - Blockade of t lymphocyte down-regulation associated with ctla-4 signaling - Google Patents
Blockade of t lymphocyte down-regulation associated with ctla-4 signaling Download PDFInfo
- Publication number
- CA2239448C CA2239448C CA2239448A CA2239448A CA2239448C CA 2239448 C CA2239448 C CA 2239448C CA 2239448 A CA2239448 A CA 2239448A CA 2239448 A CA2239448 A CA 2239448A CA 2239448 C CA2239448 C CA 2239448C
- Authority
- CA
- Canada
- Prior art keywords
- ctla
- cells
- antibody
- use according
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000011664 signaling Effects 0.000 title claims abstract description 25
- 210000001744 T-lymphocyte Anatomy 0.000 title claims description 92
- 230000003828 downregulation Effects 0.000 title description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 claims abstract description 264
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims abstract description 171
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims abstract description 171
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 96
- 102000036639 antigens Human genes 0.000 claims abstract description 73
- 108091007433 antigens Proteins 0.000 claims abstract description 73
- 239000000427 antigen Substances 0.000 claims abstract description 72
- 230000004044 response Effects 0.000 claims abstract description 49
- 238000011282 treatment Methods 0.000 claims abstract description 45
- 230000001965 increasing effect Effects 0.000 claims abstract description 22
- 230000005867 T cell response Effects 0.000 claims abstract description 18
- 210000004027 cell Anatomy 0.000 claims description 222
- 210000004881 tumor cell Anatomy 0.000 claims description 57
- 108090000623 proteins and genes Proteins 0.000 claims description 56
- 102000004169 proteins and genes Human genes 0.000 claims description 44
- 239000012634 fragment Substances 0.000 claims description 38
- 230000028993 immune response Effects 0.000 claims description 36
- 239000002269 analeptic agent Substances 0.000 claims description 23
- 102000004127 Cytokines Human genes 0.000 claims description 20
- 108010002350 Interleukin-2 Proteins 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 20
- 108090000695 Cytokines Proteins 0.000 claims description 19
- 102000000588 Interleukin-2 Human genes 0.000 claims description 19
- 238000002560 therapeutic procedure Methods 0.000 claims description 19
- 230000004614 tumor growth Effects 0.000 claims description 16
- 230000001717 pathogenic effect Effects 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 244000052769 pathogen Species 0.000 claims description 12
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 11
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 10
- 230000007423 decrease Effects 0.000 claims description 10
- 230000000890 antigenic effect Effects 0.000 claims description 8
- 231100000183 lymphotoxic Toxicity 0.000 claims description 8
- 230000001917 lymphotoxic effect Effects 0.000 claims description 8
- 241000700605 Viruses Species 0.000 claims description 7
- 201000009030 Carcinoma Diseases 0.000 claims description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 5
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 5
- 102000013462 Interleukin-12 Human genes 0.000 claims description 5
- 108010065805 Interleukin-12 Proteins 0.000 claims description 5
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 5
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 5
- 230000006052 T cell proliferation Effects 0.000 claims description 5
- 102000000589 Interleukin-1 Human genes 0.000 claims description 4
- 108010002352 Interleukin-1 Proteins 0.000 claims description 4
- 241000191940 Staphylococcus Species 0.000 claims description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 230000028327 secretion Effects 0.000 claims description 4
- 101710132601 Capsid protein Proteins 0.000 claims description 3
- 101710094648 Coat protein Proteins 0.000 claims description 3
- 101710091045 Envelope protein Proteins 0.000 claims description 3
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 claims description 3
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 claims description 3
- 101710125418 Major capsid protein Proteins 0.000 claims description 3
- 101710141454 Nucleoprotein Proteins 0.000 claims description 3
- 101710083689 Probable capsid protein Proteins 0.000 claims description 3
- 101710188315 Protein X Proteins 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 229940117681 interleukin-12 Drugs 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 239000006166 lysate Substances 0.000 claims description 2
- 210000003071 memory t lymphocyte Anatomy 0.000 claims description 2
- 102000000646 Interleukin-3 Human genes 0.000 claims 2
- 108010002386 Interleukin-3 Proteins 0.000 claims 2
- 102100021696 Syncytin-1 Human genes 0.000 claims 2
- 229940076264 interleukin-3 Drugs 0.000 claims 2
- 230000003053 immunization Effects 0.000 abstract description 20
- 238000002649 immunization Methods 0.000 abstract description 19
- 230000005764 inhibitory process Effects 0.000 abstract description 12
- 230000006044 T cell activation Effects 0.000 abstract description 11
- 239000002671 adjuvant Substances 0.000 abstract description 9
- 230000001684 chronic effect Effects 0.000 abstract description 7
- 230000009385 viral infection Effects 0.000 abstract description 4
- 208000036142 Viral infection Diseases 0.000 abstract description 3
- 239000011230 binding agent Substances 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 62
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 56
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 56
- 235000018102 proteins Nutrition 0.000 description 41
- 241000282414 Homo sapiens Species 0.000 description 39
- 230000000694 effects Effects 0.000 description 39
- 239000002981 blocking agent Substances 0.000 description 38
- 239000007924 injection Substances 0.000 description 35
- 238000002347 injection Methods 0.000 description 35
- 241001465754 Metazoa Species 0.000 description 34
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 32
- 102000043321 human CTLA4 Human genes 0.000 description 31
- 230000035755 proliferation Effects 0.000 description 31
- 230000027455 binding Effects 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 25
- 238000000034 method Methods 0.000 description 25
- 241000699800 Cricetinae Species 0.000 description 24
- 108020001507 fusion proteins Proteins 0.000 description 24
- 102000037865 fusion proteins Human genes 0.000 description 24
- 210000002966 serum Anatomy 0.000 description 24
- 210000004408 hybridoma Anatomy 0.000 description 20
- 238000001727 in vivo Methods 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 17
- 239000012275 CTLA-4 inhibitor Substances 0.000 description 17
- 230000004913 activation Effects 0.000 description 17
- 239000012894 fetal calf serum Substances 0.000 description 17
- 230000002163 immunogen Effects 0.000 description 17
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 16
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 239000013604 expression vector Substances 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 15
- 230000001404 mediated effect Effects 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 13
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 13
- 230000003993 interaction Effects 0.000 description 13
- 210000004698 lymphocyte Anatomy 0.000 description 13
- 230000004927 fusion Effects 0.000 description 12
- 210000001165 lymph node Anatomy 0.000 description 12
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 11
- 239000002299 complementary DNA Substances 0.000 description 11
- 230000012010 growth Effects 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 230000000638 stimulation Effects 0.000 description 11
- 101000859077 Mus musculus Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 10
- 230000000903 blocking effect Effects 0.000 description 10
- 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
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 230000004073 interleukin-2 production Effects 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 9
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 8
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 8
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 8
- 230000030833 cell death Effects 0.000 description 8
- 239000006285 cell suspension Substances 0.000 description 8
- 230000004940 costimulation Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 238000007912 intraperitoneal administration Methods 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000011725 BALB/c mouse Methods 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 241000191967 Staphylococcus aureus Species 0.000 description 7
- 150000001413 amino acids Chemical group 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 7
- 238000010348 incorporation Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 238000012933 kinetic analysis Methods 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 239000004005 microsphere Substances 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 206010009944 Colon cancer Diseases 0.000 description 6
- 201000008808 Fibrosarcoma Diseases 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 230000000735 allogeneic effect Effects 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012228 culture supernatant Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 229940104230 thymidine Drugs 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 238000013357 binding ELISA Methods 0.000 description 5
- 230000006369 cell cycle progression Effects 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000002516 postimmunization Effects 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 210000004988 splenocyte Anatomy 0.000 description 5
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Natural products CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 108010045634 B7 Antigens Proteins 0.000 description 4
- 102000005738 B7 Antigens Human genes 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 4
- 229930182566 Gentamicin Natural products 0.000 description 4
- 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 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 244000309466 calf Species 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 238000003306 harvesting Methods 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 231100000617 superantigen Toxicity 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 3
- 101100222220 Mus musculus Ctla4 gene Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108020005067 RNA Splice Sites Proteins 0.000 description 3
- 239000006146 Roswell Park Memorial Institute 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
- 108091008874 T cell receptors Proteins 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000007503 antigenic stimulation Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- -1 dipstick Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 239000004816 latex Substances 0.000 description 3
- 229920000126 latex Polymers 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000002831 pharmacologic agent Substances 0.000 description 3
- 210000004180 plasmocyte Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009696 proliferative response Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 239000006152 selective media Substances 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 229940054269 sodium pyruvate Drugs 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 2
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 2
- 101150106931 IFNG gene Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102100034256 Mucin-1 Human genes 0.000 description 2
- 108010008707 Mucin-1 Proteins 0.000 description 2
- 241001045988 Neogene Species 0.000 description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102000004140 Oncostatin M Human genes 0.000 description 2
- 108090000630 Oncostatin M Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000003679 cervix uteri Anatomy 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000002222 downregulating effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 2
- 229960002455 methoxyflurane Drugs 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 230000001114 myogenic effect Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 101150091879 neo gene Proteins 0.000 description 2
- 230000000955 neuroendocrine Effects 0.000 description 2
- 201000011519 neuroendocrine tumor Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 238000012342 propidium iodide staining Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 210000001350 reed-sternberg cell Anatomy 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 235000004400 serine Nutrition 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- VUYXVWGKCKTUMF-UHFFFAOYSA-N tetratriacontaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO VUYXVWGKCKTUMF-UHFFFAOYSA-N 0.000 description 2
- 230000001573 trophoblastic effect Effects 0.000 description 2
- 208000029387 trophoblastic neoplasm Diseases 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- UHEPSJJJMTWUCP-DHDYTCSHSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-[(1r)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N UHEPSJJJMTWUCP-DHDYTCSHSA-N 0.000 description 1
- 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 1
- ZTOJFFHGPLIVKC-UHFFFAOYSA-N 3-ethyl-2-[(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C1=NN=C1SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-UHFFFAOYSA-N 0.000 description 1
- HQFLTUZKIRYQSP-UHFFFAOYSA-N 3-ethyl-2h-1,3-benzothiazole-6-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2N(CC)CSC2=C1 HQFLTUZKIRYQSP-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 108010035053 B7-1 Antigen Proteins 0.000 description 1
- 102000038504 B7-1 Antigen Human genes 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 102100036912 Desmin Human genes 0.000 description 1
- 108010044052 Desmin Proteins 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000250507 Gigaspora candida Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101100061678 Homo sapiens CTLA4 gene Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102100033421 Keratin, type I cytoskeletal 18 Human genes 0.000 description 1
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 1
- 102100023972 Keratin, type II cytoskeletal 8 Human genes 0.000 description 1
- 108010066327 Keratin-18 Proteins 0.000 description 1
- 108010066302 Keratin-19 Proteins 0.000 description 1
- 108010070511 Keratin-8 Proteins 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000283953 Lagomorpha Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 108090000143 Mouse Proteins Proteins 0.000 description 1
- 101000914483 Mus musculus T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000005890 Neuroma Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000029033 Spinal Cord disease Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000004874 Synaptophysin Human genes 0.000 description 1
- 108090001076 Synaptophysin Proteins 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000011024 colonic benign neoplasm Diseases 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 210000005045 desmin Anatomy 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000005584 early death Effects 0.000 description 1
- 230000000459 effect on growth Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 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
- 239000005338 frosted glass Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 102000054189 human CD80 Human genes 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000003810 lymphokine-activated killer cell Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 230000007896 negative regulation of T cell activation Effects 0.000 description 1
- 230000025020 negative regulation of T cell proliferation Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 230000020402 negative regulation of interleukin-2 secretion Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 108010031345 placental alkaline phosphatase Proteins 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012809 post-inoculation Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 210000002105 tongue Anatomy 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- 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
-
- 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
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/81—Drug, bio-affecting and body treating compositions involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Radiation-Therapy Devices (AREA)
- External Artificial Organs (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2770851A CA2770851C (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/566,853 US5855887A (en) | 1995-07-25 | 1995-12-04 | Blockade of lymphocyte down-regulation associated with CTLA-4 signaling |
| US08/566,853 | 1995-12-04 | ||
| US08/646,605 | 1996-05-08 | ||
| US08/646,605 US5811097A (en) | 1995-07-25 | 1996-05-08 | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| PCT/US1996/019375 WO1997020574A1 (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2770851A Division CA2770851C (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2239448A1 CA2239448A1 (en) | 1997-06-12 |
| CA2239448C true CA2239448C (en) | 2013-10-01 |
Family
ID=27074292
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2239448A Expired - Lifetime CA2239448C (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
| CA2770851A Expired - Lifetime CA2770851C (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2770851A Expired - Lifetime CA2770851C (en) | 1995-12-04 | 1996-12-04 | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US5811097A (enExample) |
| EP (3) | EP0865293B1 (enExample) |
| JP (2) | JP4477701B2 (enExample) |
| AT (1) | ATE415172T1 (enExample) |
| AU (1) | AU730500B2 (enExample) |
| CA (2) | CA2239448C (enExample) |
| DE (2) | DE69637762D1 (enExample) |
| DK (2) | DK0865293T3 (enExample) |
| ES (2) | ES2318853T3 (enExample) |
| LU (1) | LU91927I2 (enExample) |
| PT (2) | PT865293E (enExample) |
| WO (1) | WO1997020574A1 (enExample) |
Families Citing this family (513)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7820798B2 (en) * | 1994-11-07 | 2010-10-26 | Human Genome Sciences, Inc. | Tumor necrosis factor-gamma |
| US7597886B2 (en) * | 1994-11-07 | 2009-10-06 | Human Genome Sciences, Inc. | Tumor necrosis factor-gamma |
| US7429646B1 (en) | 1995-06-05 | 2008-09-30 | Human Genome Sciences, Inc. | Antibodies to human tumor necrosis factor receptor-like 2 |
| US6051227A (en) * | 1995-07-25 | 2000-04-18 | The Regents Of The University Of California, Office Of Technology Transfer | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US7888466B2 (en) | 1996-01-11 | 2011-02-15 | Human Genome Sciences, Inc. | Human G-protein chemokine receptor HSATU68 |
| US7964190B2 (en) * | 1996-03-22 | 2011-06-21 | Human Genome Sciences, Inc. | Methods and compositions for decreasing T-cell activity |
| US6635743B1 (en) | 1996-03-22 | 2003-10-21 | Human Genome Sciences, Inc. | Apoptosis inducing molecule II and methods of use |
| US20060034844A1 (en) * | 1996-12-04 | 2006-02-16 | The Regents Of The University Of California | Stimulation of T cells against self antigens using CTLA-4 blocking agents |
| WO1998042752A1 (en) * | 1997-03-21 | 1998-10-01 | Brigham And Women's Hospital Inc. | Immunotherapeutic ctla-4 binding peptides |
| US6429286B1 (en) * | 1997-04-16 | 2002-08-06 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Immunoregulatory molecules for costimulatory signal transduction |
| EP1982990A1 (en) | 1998-03-19 | 2008-10-22 | Human Genome Sciences, Inc. | Cytokine receptor common gamma chain like |
| JP5341287B2 (ja) * | 1998-12-03 | 2013-11-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ctla−4遮断薬を用いる自己抗原に対するt細胞の刺激 |
| EE05627B1 (et) * | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
| US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
| ES2706547T3 (es) | 1998-12-23 | 2019-03-29 | Pfizer | Anticuerpos monoclonales humanos para CTLA-4 |
| WO2000050620A2 (en) | 1999-02-26 | 2000-08-31 | Human Genome Sciences, Inc. | Human endokine alpha and methods of use |
| WO2001014424A2 (en) | 1999-08-24 | 2001-03-01 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| EP1803730A1 (en) | 2000-04-12 | 2007-07-04 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7700359B2 (en) * | 2000-06-02 | 2010-04-20 | Novartis Vaccines And Diagnostics, Inc. | Gene products differentially expressed in cancerous cells |
| AU2001282856A1 (en) | 2000-06-15 | 2001-12-24 | Human Genome Sciences, Inc. | Human tumor necrosis factor delta and epsilon |
| EP1683865A3 (en) | 2001-02-02 | 2006-10-25 | Eli Lilly & Company | Mammalian proteins and in particular CD200 |
| CA2437811A1 (en) | 2001-02-09 | 2002-08-22 | Human Genome Sciences, Inc. | Human g-protein chemokine receptor (ccr5) hdgnr10 |
| WO2002083704A1 (en) | 2001-04-13 | 2002-10-24 | Human Genome Sciences, Inc. | Vascular endothelial growth factor 2 |
| IL149701A0 (en) * | 2001-05-23 | 2002-11-10 | Pfizer Prod Inc | Use of anti-ctla-4 antibodies |
| US6867189B2 (en) * | 2001-07-26 | 2005-03-15 | Genset S.A. | Use of adipsin/complement factor D in the treatment of metabolic related disorders |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| US6578724B1 (en) * | 2001-12-29 | 2003-06-17 | United States Can Company | Connector for use in packaging aerosol containers |
| ES2323456T3 (es) * | 2002-01-08 | 2009-07-16 | Novartis Vaccines And Diagnostics, Inc. | Productos genicos diferencialmente expresados en celulas de pecho cancerosas y sus metodos de uso. |
| WO2003086459A1 (en) | 2002-04-12 | 2003-10-23 | Medarex, Inc. | Methods of treatement using ctla-4 antibodies |
| RU2375077C2 (ru) * | 2002-05-02 | 2009-12-10 | Юниверсити Оф Коннектикут Хелт Сентер | Использование белков теплового шока для повышения эффективности терапий антителами |
| US7259002B2 (en) * | 2003-01-21 | 2007-08-21 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel acyl coenzyme A, monoacylglycerol acyltransferase-3 (MGAT3), and uses thereof |
| US20060246123A1 (en) * | 2003-03-12 | 2006-11-02 | Eli Gilboa | Oligonucleotide mimetics |
| JP4838720B2 (ja) | 2003-05-13 | 2011-12-14 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | 転移および転移がもたらす骨格関連現象を調節する方法 |
| US7465446B2 (en) | 2003-05-30 | 2008-12-16 | Medarex, Inc. | Surrogate therapeutic endpoint for anti-CTLA4-based immunotherapy of disease |
| EP1729795B1 (en) | 2004-02-09 | 2016-02-03 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| KR100845354B1 (ko) * | 2004-03-26 | 2008-07-09 | 화이자 프로덕츠 인코포레이티드 | 항-ctla-4 항체의 용도 |
| US7494779B2 (en) * | 2004-06-14 | 2009-02-24 | Li-Te Chin | Method for producing human antibodies to human CD152 with properties of agonist, antagonist, or inverse agonist |
| US20060057626A1 (en) * | 2004-09-03 | 2006-03-16 | Nichol Geoffrey M | Assessment of CTLA-4 polymorphisms in CTLA-4 blockade therapy |
| US20090252741A1 (en) * | 2004-09-08 | 2009-10-08 | Ohio State University Research Foundation | Human monoclonal anti-ctla4 antibodies in cancer treatment |
| AR053690A1 (es) * | 2005-03-23 | 2007-05-16 | Pfizer Prod Inc | Terapia de cancer de prostata con anticuerpos contra ctla4 y terapia hormonal |
| AU2006227880A1 (en) * | 2005-03-23 | 2006-09-28 | Pfizer Products Inc. | Anti-CTLA4 antibody and indolinone combination therapy for treatment of cancer |
| EP1896582A4 (en) * | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES AGAINST PROGRAMMED CELL DEATH 1 (PD-1) AND METHOD FOR CREATING TREATMENT WITH ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS |
| US20070054360A1 (en) | 2005-05-12 | 2007-03-08 | Zeren Gao | Compositions and methods for modulating immune responses |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| WO2007010394A2 (en) | 2005-07-19 | 2007-01-25 | Stemgen S.P.A. | Inhibition of the tumorigenic potential of tumor stem cells by lif and bmps |
| US20070072247A1 (en) * | 2005-08-31 | 2007-03-29 | Academia Sinica | Methods and reagents for the analysis and purification of polysaccharides |
| US7943134B2 (en) | 2005-08-31 | 2011-05-17 | Academia Sinica | Compositions and methods for identifying response targets and treating flavivirus infection responses |
| EA015860B1 (ru) | 2005-10-13 | 2011-12-30 | Хьюман Дженом Сайенсиз, Инк. | Способы лечения аутоиммунных заболеваний при использовании антагониста нейтрокина-альфа |
| EP1945261A4 (en) | 2005-11-07 | 2010-05-12 | Scripps Research Inst | COMPOSITIONS AND METHODS FOR CONTROLLING THE SPECIFICITY OF TISSUE FACTOR SIGNALING |
| US7611702B2 (en) * | 2005-11-08 | 2009-11-03 | Medarex, Inc. | TNF-alpha blocker treatment for enterocolitis associated with immunostimulatory therapeutic antibody therapy |
| EP1954311A4 (en) | 2005-12-07 | 2009-12-23 | Medarex Inc | CTLA-4 ANTIBODY DOSAGE ESCALATION THERAPY |
| EP2013348A4 (en) * | 2006-03-30 | 2009-09-02 | Univ California | METHOD AND COMPOSITIONS FOR LOCALIZED SECRETION OF ANTI-CTLA-4 ANTIBODIES |
| US7572618B2 (en) | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
| NZ577085A (en) | 2006-11-15 | 2012-06-29 | Medarex Inc | Human monoclonal antibodies to btla and methods of use |
| WO2008109075A2 (en) * | 2007-03-05 | 2008-09-12 | Bristol-Myers Squibb Company | Biomarkers and methods for determining sensitivity to ctla-4 antagonists |
| WO2008112192A2 (en) * | 2007-03-08 | 2008-09-18 | Kalobios Pharmaceuticals, Inc. | Epha3 antibodies for the treatment of solid tumors |
| US7968300B2 (en) * | 2007-11-21 | 2011-06-28 | Li-Te Chin | Method of isolating regulatory T cells from human samples |
| ES2558568T3 (es) | 2008-01-08 | 2016-02-05 | Bristol-Myers Squibb Company | Combinación de anticuerpo anti-CTLA4 con agentes moduladores de la tubulina para el tratamiento de enfermedades proliferativas |
| DE202008000834U1 (de) | 2008-01-21 | 2008-05-29 | Chin, Li-Te | Zusammensetzung und Reagenz für CTLA-4 und Verwendungen derselben |
| US20110020368A1 (en) | 2008-03-25 | 2011-01-27 | Nancy Hynes | Treating cancer by down-regulating frizzled-4 and/or frizzled-1 |
| MX2010012579A (es) * | 2008-05-29 | 2010-12-20 | Squibb Bristol Myers Co | Metodos para predecir respuesta de pacientes a modulacion de la via co-estimuladora. |
| US8119129B2 (en) | 2008-08-01 | 2012-02-21 | Bristol-Myers Squibb Company | Combination of anti-CTLA4 antibody with dasatinib for the treatment of proliferative diseases |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| WO2010042433A1 (en) | 2008-10-06 | 2010-04-15 | Bristol-Myers Squibb Company | Combination of cd137 antibody and ctla-4 antibody for the treatment of proliferative diseases |
| EP2241323A1 (en) | 2009-04-14 | 2010-10-20 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Research | Tenascin-W and brain cancers |
| US20100297072A1 (en) * | 2009-05-19 | 2010-11-25 | Depinho Ronald A | Combinations of Immunostimulatory Agents, Oncolytic Virus, and Additional Anticancer Therapy |
| DK2769737T3 (en) | 2009-07-20 | 2017-07-24 | Bristol Myers Squibb Co | COMBINATION OF ANTI-CTLA4 ANTIBODY WITH ETOPOSIDE FOR SYNERGISTIC TREATMENT OF PROLIFERATIVE DISEASES |
| EP2292266A1 (en) | 2009-08-27 | 2011-03-09 | Novartis Forschungsstiftung, Zweigniederlassung | Treating cancer by modulating copine III |
| US20120244170A1 (en) | 2009-09-22 | 2012-09-27 | Rafal Ciosk | Treating cancer by modulating mex-3 |
| WO2011045352A2 (en) | 2009-10-15 | 2011-04-21 | Novartis Forschungsstiftung | Spleen tyrosine kinase and brain cancers |
| US20120213801A1 (en) | 2009-10-30 | 2012-08-23 | Ekaterina Gresko | Phosphorylated Twist1 and cancer |
| WO2011107586A1 (en) | 2010-03-05 | 2011-09-09 | Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute For Biomedical Research, | Smoc1, tenascin-c and brain cancers |
| US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
| US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
| EP2552947A4 (en) | 2010-03-26 | 2013-11-13 | Dartmouth College | VISTA REGULATORY T CELL MEDIATOR PROTEIN, VISTA BINDING ACTIVE SUBSTANCES AND USE THEREOF |
| US20130034543A1 (en) | 2010-04-19 | 2013-02-07 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Resear | Modulating xrn1 |
| US20130064831A1 (en) | 2010-05-17 | 2013-03-14 | Bristol-Myers Squibb Company | Immunotherapeutic dosing regimens and combinations thereof |
| US20130089538A1 (en) | 2010-06-10 | 2013-04-11 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute forBiomedical Researh | Treating cancer by modulating mammalian sterile 20-like kinase 3 |
| WO2012032143A1 (en) | 2010-09-10 | 2012-03-15 | Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute For Biomedical Research | Phosphorylated twist1 and metastasis |
| EP2712655B1 (en) | 2011-04-28 | 2019-12-18 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
| WO2012168259A1 (en) | 2011-06-06 | 2012-12-13 | Novartis Forschungsstiftung, Zweigniederlassung | Protein tyrosine phosphatase, non-receptor type 11 (ptpn11) and triple-negative breast cancer |
| EP2591796A1 (en) * | 2011-11-10 | 2013-05-15 | Universität Zürich | Combination medicament comprising IL-12 and an anti-CTLA-4 ligand for tumor therapy |
| US11951157B2 (en) | 2011-10-11 | 2024-04-09 | Universitat Zurich | Methods of treating malignant tumour with IL-12 and anti-PD-1 antibody |
| WO2013053775A1 (en) * | 2011-10-11 | 2013-04-18 | Universität Zürich Prorektorat Mnw | Combination medicament comprising il-12 and an agent for blockade of t-cell inhibitory molecules for tumour therapy |
| US20140314787A1 (en) | 2011-11-08 | 2014-10-23 | Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute | Treatment for neurodegenerative diseases |
| WO2013068432A1 (en) | 2011-11-08 | 2013-05-16 | Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute For Biomedical Research | Early diagnostic of neurodegenerative diseases |
| WO2013102825A1 (en) | 2012-01-02 | 2013-07-11 | Novartis Ag | Cdcp1 and breast cancer |
| US20150110779A1 (en) | 2012-03-15 | 2015-04-23 | Bristol-Myers Squibb Company | Methods for predicting gastrointestinal immune-related adverse events (gi-irae) in patients treated with modulation of the co-stimulatory pathway |
| US20150079100A1 (en) | 2012-03-23 | 2015-03-19 | Bristol-Myers Squibb Company | Methods of treatments using ctla-4 antibodies |
| EP2831112A1 (en) | 2012-03-29 | 2015-02-04 | Friedrich Miescher Institute for Biomedical Research | Inhibition of interleukin- 8 and/or its receptor cxcrl in the treatment her2/her3 -overexpressing breast cancer |
| US20150118244A1 (en) | 2012-05-10 | 2015-04-30 | Bristol-Myers Squibb Company | Anti-tumor antibodies as predictive or prognostic biomarkers of efficacy and survival in ipilimumab-treated patients |
| DK3421486T5 (da) | 2012-06-22 | 2024-09-16 | The Trustees Of Darthmouth College | Nye Vista-IG-konstruktioner og anvendelse af Vista-IG til behandling af autoimmune, allergiske og inflammatoriske lidelser |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| US20150218238A1 (en) | 2012-06-29 | 2015-08-06 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Resear | Treating diseases by modulating a specific isoform of mkl1 |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| EP2870242A1 (en) | 2012-07-05 | 2015-05-13 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Research | New treatment for neurodegenerative diseases |
| WO2014006115A1 (en) | 2012-07-06 | 2014-01-09 | Novartis Ag | Combination of a phosphoinositide 3-kinase inhibitor and an inhibitor of the il-8/cxcr interaction |
| US9790184B2 (en) | 2012-07-27 | 2017-10-17 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
| CN104704002B (zh) | 2012-08-30 | 2022-05-10 | 安姆根有限公司 | 使用单纯疱疹病毒和免疫检查点抑制剂治疗黑色素瘤的方法 |
| CA2884704C (en) | 2012-09-07 | 2023-04-04 | Randolph J. Noelle | Vista modulators for diagnosis and treatment of cancer |
| EA030573B1 (ru) | 2013-01-02 | 2018-08-31 | Дикой Байосистемз, Инк. | Композиции и способы для лечения рака с применением бактерий |
| US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
| EP3030902B1 (en) | 2013-08-07 | 2019-09-25 | Friedrich Miescher Institute for Biomedical Research | New screening method for the treatment friedreich's ataxia |
| MX374291B (es) | 2013-08-08 | 2025-03-06 | Cytune Pharma | Modulocinas basadas en dominio sushi de interleucina-15 (il-15) y receptor alfa de interleucina-15 (il-15ra). |
| HUE046964T2 (hu) | 2013-08-08 | 2020-04-28 | Cytune Pharma | Kombinált gyógyászati készítmény |
| US10081681B2 (en) | 2013-09-20 | 2018-09-25 | Bristol-Myers Squibb Company | Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors |
| EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
| EP3065772B1 (en) | 2013-11-05 | 2024-07-24 | Cognate Bioservices, Inc. | Combinations of checkpoint inhibitors and therapeutics to treat cancer |
| US20160264670A1 (en) | 2013-11-06 | 2016-09-15 | Bristol-Myers Squibb Company | Immunotherapeutic dosing regimens and combinations thereof |
| IL301714A (en) | 2013-12-24 | 2023-05-01 | Janssen Pharmaceutica Nv | Antibodies and anti-VISTA fragments |
| US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| KR102442436B1 (ko) | 2014-03-14 | 2022-09-15 | 노파르티스 아게 | Lag-3에 대한 항체 분자 및 그의 용도 |
| US9850225B2 (en) | 2014-04-14 | 2017-12-26 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| PT3151921T (pt) | 2014-06-06 | 2019-11-21 | Bristol Myers Squibb Co | Anticorpos contra recetor do fator de necrose tumoral induzido por glicocorticoide e utilizações dos mesmos |
| MX389695B (es) | 2014-06-11 | 2025-03-20 | Kathy A Green | Uso de agonistas y antagonistas vista para suprimir o aumentar la inmunidad humoral. |
| EP3154579A1 (en) | 2014-06-13 | 2017-04-19 | Friedrich Miescher Institute for Biomedical Research | New treatment against influenza virus |
| EP3157535A1 (en) | 2014-06-23 | 2017-04-26 | Friedrich Miescher Institute for Biomedical Research | Methods for triggering de novo formation of heterochromatin and or epigenetic silencing with small rnas |
| US20170165261A1 (en) | 2014-07-01 | 2017-06-15 | Brian Arthur Hemmings | Combination of a brafv600e inhibitor and mertk inhibitor to treat melanoma |
| EP3552615B8 (en) | 2014-07-16 | 2022-03-02 | Transgene | Oncolytic virus for expression of immune checkpoint modulators |
| DK3169340T3 (da) | 2014-07-16 | 2020-11-09 | Roussy Inst Gustave | Kombination af onkolytisk virus med immun-checkpoint-modulatorer |
| CN105296433B (zh) | 2014-08-01 | 2018-02-09 | 中山康方生物医药有限公司 | 一种ctla4抗体、其药物组合物及其用途 |
| JP6681905B2 (ja) | 2014-09-13 | 2020-04-15 | ノバルティス アーゲー | Alk阻害剤の併用療法 |
| EP3197557A1 (en) | 2014-09-24 | 2017-08-02 | Friedrich Miescher Institute for Biomedical Research | Lats and breast cancer |
| KR20170066546A (ko) | 2014-10-03 | 2017-06-14 | 노파르티스 아게 | 조합 요법 |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| US9732119B2 (en) | 2014-10-10 | 2017-08-15 | Bristol-Myers Squibb Company | Immunomodulators |
| EP4029508A1 (en) | 2014-10-10 | 2022-07-20 | Idera Pharmaceuticals, Inc. | Treatment of cancer using tlr9 agonists and checkpoint inhibitors |
| EA201790834A1 (ru) | 2014-10-14 | 2018-01-31 | Новартис Аг | Молекулы антител к pd-l1 и их применение |
| US9856292B2 (en) | 2014-11-14 | 2018-01-02 | Bristol-Myers Squibb Company | Immunomodulators |
| ES2807182T3 (es) | 2014-11-21 | 2021-02-22 | Bristol Myers Squibb Co | Anticuerpos frente a CD73 y sus usos |
| KR20170088984A (ko) | 2014-12-04 | 2017-08-02 | 브리스톨-마이어스 스큅 컴퍼니 | 암 (골수종)을 치료하기 위한 항-cs1 항체와 항-pd1 항체의 조합 |
| CA2969730A1 (en) | 2014-12-05 | 2016-06-09 | Immunext, Inc. | Identification of vsig8 as the putative vista receptor and its use thereof to produce vista/vsig8 modulators |
| JP6767096B2 (ja) | 2014-12-11 | 2020-10-14 | リティックス バイオファーマ エイエス | 免疫チェックポイント阻害剤の組み合わせ |
| KR102549746B1 (ko) | 2014-12-18 | 2023-07-03 | 암젠 인크 | 안정한 동결된 단순 포진 바이러스 제제 |
| US9861680B2 (en) | 2014-12-18 | 2018-01-09 | Bristol-Myers Squibb Company | Immunomodulators |
| WO2016100882A1 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Combination therapies |
| US9944678B2 (en) | 2014-12-19 | 2018-04-17 | Bristol-Myers Squibb Company | Immunomodulators |
| JP6180663B2 (ja) | 2014-12-23 | 2017-08-16 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Tigitに対する抗体 |
| CN107428818A (zh) | 2015-01-29 | 2017-12-01 | 密西根州立大学校董会 | 隐藏多肽及其用途 |
| US20160222060A1 (en) | 2015-02-04 | 2016-08-04 | Bristol-Myers Squibb Company | Immunomodulators |
| EP3256156B1 (en) | 2015-02-13 | 2025-02-12 | Transgene | Immunotherapeutic vaccine and antibody combination therapy |
| PT3258951T (pt) | 2015-02-19 | 2020-08-18 | Compugen Ltd | Anticorpos anti-pvrig e métodos de utilização |
| EA035817B1 (ru) | 2015-03-10 | 2020-08-14 | Адуро Байотек, Инк. | Композиции и способы для активации сигналинга, зависимого от "гена стимулятора интерферона" |
| WO2016146143A1 (en) | 2015-03-16 | 2016-09-22 | Amal Therapeutics Sa | Cell penetrating peptides and complexes comprising the same |
| US9809625B2 (en) | 2015-03-18 | 2017-11-07 | Bristol-Myers Squibb Company | Immunomodulators |
| CA2981068C (en) | 2015-03-26 | 2021-12-14 | Women & Infants Hospital Of Rhode Island | Therapy for malignant disease comprising the inhibition of human epididymal secretory protein e4 and immune checkpoint inhibitors |
| US11215616B2 (en) | 2015-04-10 | 2022-01-04 | National Institutes Of Health (Nih), (Dhhs), U.S. Government | Methods of determining patient populations amenable to immunomodulatory treatment of cancer |
| EP3736287A1 (en) | 2015-05-11 | 2020-11-11 | The Johns Hopkins University | Autoimmune antibodies for use in inhibiting cancer cell growth |
| SG10202002131PA (en) | 2015-05-21 | 2020-05-28 | Harpoon Therapeutics Inc | Trispecific binding proteins and methods of use |
| CA3025145A1 (en) | 2015-05-22 | 2016-12-01 | Translational Drug Development Llc | Benzamide and active compound compositions and methods of use |
| RS63897B1 (sr) | 2015-05-29 | 2023-02-28 | Bristol Myers Squibb Co | Antitela protiv ox40 i njihova primena |
| HRP20201031T1 (hr) | 2015-05-29 | 2020-10-16 | Agenus Inc. | Anti-ctla-4 protutijela i postupci njihove upotrebe |
| TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
| CN114805576A (zh) | 2015-06-24 | 2022-07-29 | 詹森药业有限公司 | 抗vista抗体和片段 |
| CA2990015A1 (en) | 2015-06-29 | 2017-01-05 | The Rockefeller University | Antibodies to cd40 with enhanced agonist activity |
| JP6754785B2 (ja) | 2015-06-29 | 2020-09-16 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 免疫治療投与レジメンおよびその組合せ |
| US10973822B2 (en) | 2015-07-02 | 2021-04-13 | Celgene Corporation | Combination therapy for treatment of hematological cancers and solid tumors |
| BR112018000917A2 (pt) | 2015-07-16 | 2018-09-11 | Bioxcel Therapeutics Inc | abordagem inovadora para o tratamento de câncer através da imunomodulação |
| CN107921087A (zh) | 2015-07-16 | 2018-04-17 | 百欧肯治疗有限公司 | 治疗癌症的组合物及方法 |
| ES2878188T3 (es) | 2015-07-29 | 2021-11-18 | Novartis Ag | Terapias de combinación que comprenden moléculas de anticuerpos contra LAG-3 |
| EP3316902A1 (en) | 2015-07-29 | 2018-05-09 | Novartis AG | Combination therapies comprising antibody molecules to tim-3 |
| US20180222982A1 (en) | 2015-07-29 | 2018-08-09 | Novartis Ag | Combination therapies comprising antibody molecules to pd-1 |
| ES2898958T3 (es) | 2015-07-30 | 2022-03-09 | Macrogenics Inc | Moléculas de unión a PD-1 y LAG-3 y métodos de uso de las mismas |
| JP7062290B2 (ja) | 2015-07-31 | 2022-05-06 | ユニバーシティー オブ フロリダ リサーチ ファンデーション, インク. | がんに対する免疫チェックポイント阻害剤との併用療法における造血幹細胞 |
| WO2017021913A1 (en) | 2015-08-04 | 2017-02-09 | Glaxosmithkline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
| EP3331919A1 (en) | 2015-08-07 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination therapy comprising anti ctla-4 antibodies |
| US11385231B2 (en) | 2015-08-27 | 2022-07-12 | Inserm (Institut National De La Sante Et De La Recherche Scientifique) | Methods for predicting the survival time of patients suffering from a lung cancer |
| RU2638457C2 (ru) | 2015-09-28 | 2017-12-13 | Общество С Ограниченной Ответственностью "Онкомакс" | Антитела, специфически связывающие рецептор 1 типа фактора роста фибробластов, применение антител для лечения онкологического заболевания, способ получения антител |
| WO2017055325A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of nk cells in a tissue sample |
| WO2017055324A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cells of monocytic origin in a tissue sample |
| WO2017055321A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of fibroblasts in a tissue sample |
| WO2017055327A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of endothelial cells in a tissue sample |
| WO2017055322A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of neutrophils in a tissue sample |
| WO2017055320A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cytotoxic lymphocytes in a tissue sample |
| WO2017055319A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of b cells in a tissue sample |
| WO2017055326A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
| WO2017060397A1 (en) | 2015-10-09 | 2017-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of subjects suffering from melanoma metastases |
| US10745382B2 (en) | 2015-10-15 | 2020-08-18 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| ES2994611T3 (en) | 2015-10-19 | 2025-01-27 | Cg Oncology Inc | Methods of treating solid or lymphatic tumors by combination therapy |
| US10149887B2 (en) | 2015-10-23 | 2018-12-11 | Canbas Co., Ltd. | Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment |
| WO2017072669A1 (en) | 2015-10-28 | 2017-05-04 | Friedrich Miescher Institute For Biomedical Research | Tenascin-w and biliary tract cancers |
| BR112018010172A2 (pt) | 2015-11-19 | 2018-11-21 | Bristol Myers Squibb Co | anticorpos contra receptor de fator de necrose de tumor induzido por glicocorticoide (gitr) e usos dos mesmos |
| MA44082A (fr) | 2015-12-14 | 2018-10-24 | Macrogenics Inc | Molécules bispécifiques présentant une immunoréactivité par rapport à pd-1 et à ctla-4 et leurs procédés d'utilisation |
| WO2017106656A1 (en) | 2015-12-17 | 2017-06-22 | Novartis Ag | Antibody molecules to pd-1 and uses thereof |
| MX382150B (es) | 2016-01-08 | 2025-03-13 | Celgene Corp | Formulaciones de 2-(4-clorofenil)-n-((2-(2,6-dioxopiperidin-3-il)-1-oxoisoindolin-5-il)metil)-2,2-difluoroacetamida. |
| MX385964B (es) | 2016-01-08 | 2025-03-18 | Celgene Corp | Formas sólidas de 2-(4-clorofenil)-n-((2-(2,6-dioxopiperidin-3-il)-1-oxoisoindolin-5-il) metil)-2,2-difluoroacetamida y sus composiciones farmacéuticas y usos. |
| TWI782395B (zh) | 2016-01-08 | 2022-11-01 | 美商西建公司 | 抗增生化合物,及其醫藥組合物及用途 |
| IL260218B2 (en) | 2016-01-11 | 2023-04-01 | Novartis Ag | Humanized monoclonal antibodies that elicit an immune response against interleukin-2, and their fusion proteins |
| US10822415B2 (en) | 2016-01-28 | 2020-11-03 | Inserm (Institut National De La Santéet De La Recherche Médicale) | Methods for enhancing the potency of the immune checkpoint inhibitors |
| JP6970099B2 (ja) | 2016-01-28 | 2021-11-24 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | ガンの処置のための方法及び医薬組成物 |
| BR112018016461A2 (pt) | 2016-02-12 | 2019-10-01 | Janssen Pharmaceutica Nv | anticorpos e fragmentos anti-vista, usos dos mesmos e métodos de identificação dos mesmos |
| CA3013333A1 (en) | 2016-02-26 | 2017-08-31 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Antibodies having specificity for btla and uses thereof |
| ES2985566T3 (es) | 2016-03-04 | 2024-11-06 | Univ Rockefeller | Anticuerpos contra CD40 con actividad agonista mejorada |
| US10143746B2 (en) | 2016-03-04 | 2018-12-04 | Bristol-Myers Squibb Company | Immunomodulators |
| SG10201913033UA (en) | 2016-03-04 | 2020-03-30 | Bristol Myers Squibb Co | Combination therapy with anti-cd73 antibodies |
| JP7208492B2 (ja) | 2016-03-10 | 2023-01-19 | シージー オンコロジー, インコーポレイテッド | 併用療法によって固形腫瘍又はリンパ系腫瘍を処置する方法 |
| WO2017160599A1 (en) | 2016-03-14 | 2017-09-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of cd300b antagonists to treat sepsis and septic shock |
| BR112018068461A2 (pt) | 2016-03-15 | 2019-01-22 | Mersana Therapeutics Inc | conjugado, composição farmacêutica, métodos para preparação de um conjugado e para alívio de um sintoma de um câncer. |
| CA3010779A1 (en) | 2016-03-16 | 2017-09-21 | Amal Therapeutics Sa | Combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, a cargo and a tlr peptide agonist for use in medicine |
| US10358463B2 (en) | 2016-04-05 | 2019-07-23 | Bristol-Myers Squibb Company | Immunomodulators |
| CN109789195A (zh) | 2016-04-13 | 2019-05-21 | 维维雅生物技术公司 | 离体bite激活的t细胞 |
| CA3020848A1 (en) | 2016-04-15 | 2017-10-19 | Janssen Pharmaceuticals, Inc. | Anti-human vista antibodies and use thereof |
| US20190298824A1 (en) | 2016-05-04 | 2019-10-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv | Albumin-binding immunomodulatory compositions and methods of use thereof |
| CN109195621A (zh) | 2016-05-18 | 2019-01-11 | 莫得纳特斯公司 | 编码白细胞介素12(il12)的多核苷酸及其用途 |
| WO2017201432A2 (en) | 2016-05-19 | 2017-11-23 | Jounaidi Youssef | Tethered interleukin-2 to its receptor il-2rbeta, a platform to enhance natural killer and regulatory t cell activity |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| JP7563872B2 (ja) | 2016-05-25 | 2024-10-08 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 癌を処置するための方法及び組成物 |
| CA3026054A1 (en) | 2016-05-30 | 2017-12-07 | Geovax Inc. | Compositions and methods for generating an immune response to hepatitis b virus |
| CA3028718A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| RU2021127872A (ru) | 2016-06-30 | 2021-11-09 | Онкорус, Инк. | Доставка терапевтических полипептидов посредством псевдотипированных онколитических вирусов |
| WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| ES2895066T3 (es) | 2016-07-08 | 2022-02-17 | Bristol Myers Squibb Co | Derivados de 1,3-dihidroxi-fenilo útiles como inmunomoduladores |
| WO2018011166A2 (en) | 2016-07-12 | 2018-01-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
| EP4512829A3 (en) | 2016-07-14 | 2025-06-11 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
| US11649289B2 (en) | 2016-08-04 | 2023-05-16 | Glaxosmithkline Intellectual Property Development Limited | Anti-ICOS and anti-PD-1 antibody combination therapy |
| WO2018029336A1 (en) | 2016-08-12 | 2018-02-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for determining whether a subject was administered with an activator of the ppar beta/delta pathway. |
| US11225689B2 (en) | 2016-08-17 | 2022-01-18 | The Broad Institute, Inc. | Method for determination and identification of cell signatures and cell markers |
| AU2017313085B2 (en) | 2016-08-19 | 2024-06-20 | Beone Medicines I Gmbh | Use of a combination comprising a Btk inhibitor for treating cancers |
| WO2018035710A1 (en) | 2016-08-23 | 2018-03-01 | Akeso Biopharma, Inc. | Anti-ctla4 antibodies |
| US10144706B2 (en) | 2016-09-01 | 2018-12-04 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| US11096924B2 (en) | 2016-09-07 | 2021-08-24 | Trustees Of Tufts College | Combination therapies using immuno-dash inhibitors and PGE2 antagonists |
| WO2018046736A1 (en) | 2016-09-12 | 2018-03-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from cancer |
| WO2018046738A1 (en) | 2016-09-12 | 2018-03-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from cancer |
| DK3515476T3 (da) | 2016-09-21 | 2024-09-02 | Amal Therapeutics Sa | Fusion der omfatter et cellepenetrerende peptid, en multiepitop og en trl-peptidagnost til behandlingen af cancer |
| WO2018055080A1 (en) | 2016-09-22 | 2018-03-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for reprograming immune environment in a subject in need thereof |
| US11673971B2 (en) | 2016-09-23 | 2023-06-13 | Marengo Therapeutics, Inc. | Multispecific antibody molecules comprising lambda and kappa light chains |
| WO2018067991A1 (en) | 2016-10-07 | 2018-04-12 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
| KR102526034B1 (ko) | 2016-11-07 | 2023-04-25 | 브리스톨-마이어스 스큅 컴퍼니 | 면역조정제 |
| WO2018087391A1 (en) | 2016-11-14 | 2018-05-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating stem cells proliferation or differentiation |
| US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
| CN110234319B (zh) | 2016-11-23 | 2022-09-27 | 转化药物开发有限责任公司 | 苯甲酰胺和活性化合物的组合物及其使用方法 |
| BR112019010878A2 (pt) | 2016-11-29 | 2019-10-01 | Lindhofer Horst | combinação de anticorpos multifuncionais de redirecionamento de células t com moduladores de ponto de verificação imunológico e usos dos mesmos |
| JP2020500878A (ja) | 2016-12-01 | 2020-01-16 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 併用療法 |
| CN110234342A (zh) | 2016-12-01 | 2019-09-13 | 葛兰素史密斯克莱知识产权发展有限公司 | 组合疗法 |
| US11013802B2 (en) | 2016-12-07 | 2021-05-25 | Agenus Inc. | Anti-CTLA-4 antibodies and methods of use thereof |
| WO2018112360A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating cancer |
| KR102599339B1 (ko) | 2016-12-20 | 2023-11-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역조정제로서 유용한 화합물 |
| CA3047508A1 (en) | 2016-12-23 | 2018-06-28 | Virttu Biologics Limited | Treatment of cancer |
| WO2018122249A1 (en) | 2016-12-28 | 2018-07-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from a microsatellite stable colorectal cancer |
| WO2018123999A1 (ja) | 2016-12-28 | 2018-07-05 | 学校法人近畿大学 | 免疫チェックポイント阻害剤の投与対象となる個体の選択方法 |
| WO2018122245A1 (en) | 2016-12-28 | 2018-07-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of predicting the survival time of patients suffering from cms3 colorectal cancer |
| EP3572429A4 (en) | 2017-01-23 | 2021-04-07 | Suzhou Alphamab Co., Ltd | POLYPEPTIDE OR COMPOSITE BINDER PD-L1 |
| WO2018140671A1 (en) | 2017-01-27 | 2018-08-02 | Celgene Corporation | 3-(1-oxo-4-((4-((3-oxomorpholino) methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione and isotopologues thereof |
| WO2018146128A1 (en) | 2017-02-07 | 2018-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Detection of kit polymorphism for predicting the response to checkpoint blockade cancer immunotherapy |
| EP3579885A4 (en) | 2017-02-07 | 2020-12-16 | Nantcell, Inc. | MAXIMIZING T CELL MEMORY, COMPOSITIONS AND RELATED METHODS |
| WO2018146148A1 (en) | 2017-02-07 | 2018-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A method for predicting the response to checkpoint blockade cancer immunotherapy |
| WO2018151820A1 (en) | 2017-02-16 | 2018-08-23 | Elstar Therapeutics, Inc. | Multifunctional molecules comprising a trimeric ligand and uses thereof |
| WO2018160538A1 (en) | 2017-02-28 | 2018-09-07 | Mersana Therapeutics, Inc. | Combination therapies of her2-targeted antibody-drug conjugates |
| WO2018160536A1 (en) | 2017-02-28 | 2018-09-07 | Bristol-Myers Squibb Company | Use of anti-ctla-4 antibodies with enhanced adcc to enhance immune response to a vaccine |
| WO2018167780A1 (en) | 2017-03-12 | 2018-09-20 | Yeda Research And Development Co. Ltd. | Methods of prognosing and treating cancer |
| US20200150125A1 (en) | 2017-03-12 | 2020-05-14 | Yeda Research And Development Co., Ltd. | Methods of diagnosing and prognosing cancer |
| EP3595690A1 (en) | 2017-03-15 | 2020-01-22 | Amgen Inc. | Use of oncolytic viruses, alone or in combination with a checkpoint inhibitor, for the treatment of cancer |
| WO2018175924A1 (en) | 2017-03-24 | 2018-09-27 | The Broad Institute, Inc. | Methods and compositions for regulating innate lymphoid cell inflammatory responses |
| JP7150745B2 (ja) | 2017-03-27 | 2022-10-11 | ブリストル-マイヤーズ スクイブ カンパニー | 免疫調節剤としての置換イソキノリン誘導体 |
| WO2018183921A1 (en) | 2017-04-01 | 2018-10-04 | The Broad Institute, Inc. | Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer |
| EP3606960A1 (en) | 2017-04-03 | 2020-02-12 | Oncologie, Inc. | Methods for treating cancer using ps-targeting antibodies with immuno-oncology agents |
| JP2020517256A (ja) | 2017-04-19 | 2020-06-18 | エルスター セラピューティクス, インコーポレイテッド | 多重特異性分子およびその使用 |
| US20200085891A1 (en) | 2017-04-21 | 2020-03-19 | Sillajen, Inc | Oncolytic vaccinia virus and checkpoint inhibitor combination therapy |
| EP3615566B1 (en) | 2017-04-28 | 2023-12-20 | Marengo Therapeutics, Inc. | Multispecific molecules comprising a non-immunoglobulin heterodimerization domain and uses thereof |
| UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
| CN110678750A (zh) | 2017-04-28 | 2020-01-10 | 美国默沙东药厂 | 用于癌症治疗的生物标志物 |
| WO2018209324A2 (en) | 2017-05-11 | 2018-11-15 | The Broad Institute, Inc. | Methods and compositions of use of cd8+ tumor infiltrating lymphocyte subtypes and gene signatures thereof |
| CN121159691A (zh) | 2017-05-12 | 2025-12-19 | 哈普恩治疗公司 | 间皮素结合蛋白质 |
| IL322104A (en) | 2017-05-30 | 2025-09-01 | Bristol Myers Squibb Co | Treatment of lag-3 positive tumors |
| WO2018222722A2 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
| EP3630836A1 (en) | 2017-05-31 | 2020-04-08 | Elstar Therapeutics, Inc. | Multispecific molecules that bind to myeloproliferative leukemia (mpl) protein and uses thereof |
| CA3065929A1 (en) | 2017-06-01 | 2018-12-06 | Michael Wayne SAVILLE | Bispecific antibodies that bind cd123 and cd3 |
| WO2018223004A1 (en) | 2017-06-01 | 2018-12-06 | Xencor, Inc. | Bispecific antibodies that bind cd20 and cd3 |
| EP4461825A3 (en) | 2017-06-09 | 2024-11-20 | Providence Health & Services - Oregon | Tumor-infiltrating t-cells for use in the treatment of cancer |
| WO2018232230A1 (en) * | 2017-06-15 | 2018-12-20 | Cancer Advances Inc. | Compositions and methods for inducing humoral and cellular immunities against tumors and cancer |
| US20200147099A1 (en) | 2017-06-20 | 2020-05-14 | Institut Curie | Inhibitor of suv39h1 histone methyltransferase for use in cancer combination therapy |
| EA202090103A1 (ru) | 2017-06-22 | 2020-04-24 | Селджин Корпорейшн | Лечение гепатоцеллюлярной карциномы, которая характеризуется вирусной инфекцией гепатита b |
| KR102735038B1 (ko) | 2017-06-23 | 2024-11-28 | 브리스톨-마이어스 스큅 컴퍼니 | Pd-1의 길항제로서 작용하는 면역조정제 |
| EP3644999B1 (en) | 2017-06-30 | 2022-12-14 | Celgene Corporation | Compositions and methods of use of 2-(4-chlorophenyl)-n-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl) methyl) -2,2-difluoroacetamide |
| KR102656934B1 (ko) | 2017-07-10 | 2024-04-16 | 셀진 코포레이션 | 항증식성 화합물 및 이의 사용 방법 |
| US12049643B2 (en) | 2017-07-14 | 2024-07-30 | The Broad Institute, Inc. | Methods and compositions for modulating cytotoxic lymphocyte activity |
| US12105089B2 (en) | 2017-07-17 | 2024-10-01 | The Broad Institute, Inc. | Cell atlas of the healthy and ulcerative colitis human colon |
| US11926664B2 (en) | 2017-07-25 | 2024-03-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating monocytopoiesis |
| WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
| US20210060158A1 (en) | 2017-09-19 | 2021-03-04 | Institut Curie | Agonist of aryl hydrocarbon receptor for use in cancer combination therapy |
| WO2019070755A1 (en) | 2017-10-02 | 2019-04-11 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTING AND MODULATING A GENETIC SIGNATURE OF IMMUNOTHERAPY RESISTANCE IN CANCER |
| EP3692053A1 (en) | 2017-10-03 | 2020-08-12 | Bristol-Myers Squibb Company | Immunomodulators |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| EA202090817A1 (ru) | 2017-10-13 | 2020-09-08 | Харпун Терапьютикс, Инк. | Триспецифические белки и способы их применения |
| WO2019079362A1 (en) | 2017-10-16 | 2019-04-25 | Massachusetts Institute Of Technology | HOST-PATHOGENIC INTERACTION OF MYCOBACTERIUM TUBERCULOSIS |
| WO2019077062A1 (en) | 2017-10-18 | 2019-04-25 | Vivia Biotech, S.L. | C-CELLS ACTIVATED BY BIT |
| MX2020004531A (es) | 2017-11-03 | 2020-08-03 | Aurigene Discovery Tech Ltd | Inhibidores dobles de tim-3 y las vias de pd-1. |
| EP3706798A1 (en) | 2017-11-06 | 2020-09-16 | Aurigene Discovery Technologies Limited | Conjoint therapies for immunomodulation |
| WO2019094983A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods and compositions for treating cancer by targeting the clec2d-klrb1 pathway |
| WO2019094955A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods and compositions for targeting developmental and oncogenic programs in h3k27m gliomas |
| US11679148B2 (en) | 2017-11-24 | 2023-06-20 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Methods and compositions for treating cancers |
| WO2019104289A1 (en) | 2017-11-27 | 2019-05-31 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
| JP7348899B2 (ja) | 2017-12-08 | 2023-09-21 | マレンゴ・セラピューティクス,インコーポレーテッド | 多重特異性分子及びその使用 |
| MX2020006372A (es) | 2017-12-19 | 2020-09-03 | Univ Rockefeller | Variantes de dominio de fc de igg humana con funcion efectora mejorada. |
| EP3727463A1 (en) | 2017-12-21 | 2020-10-28 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
| KR102813744B1 (ko) | 2017-12-27 | 2025-05-28 | 브리스톨-마이어스 스큅 컴퍼니 | 항-cd40 항체 및 그의 용도 |
| EP3731850A4 (en) | 2017-12-29 | 2021-12-01 | Oncorus, Inc. | ONCOLYTIC VIRUS DELIVERY OF THERAPEUTIC POLYPEPTIDES |
| EP3737692A4 (en) | 2018-01-09 | 2021-09-29 | Elstar Therapeutics, Inc. | CALRETICULIN AND MODIFIED T-LYMPHOCYTES BINDING CONSTRUCTIONS FOR THE TREATMENT OF DISEASES |
| WO2019140229A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
| JP2021510733A (ja) | 2018-01-12 | 2021-04-30 | ケーディーエーシー セラピューティクス,インコーポレーテッドKdac Therapeutics, Inc. | がんの処置のための選択的ヒストンデアセチラーゼ3(hdac3)インヒビターと免疫治療剤との組み合わせ |
| US11414418B2 (en) | 2018-01-23 | 2022-08-16 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| EP3759093B1 (en) | 2018-03-01 | 2022-11-30 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| CN111867679A (zh) | 2018-03-06 | 2020-10-30 | 居里研究所 | 用于癌症联合治疗的setdb1组蛋白甲基转移酶抑制剂 |
| RU2020133451A (ru) | 2018-03-12 | 2022-04-12 | Инститьют Насьонал Де Ла Санте Et De La Решерш Медикаль (Инсерм) | Применение терапевтически эффективной комбинации химиотерапиии и ингибитора контрольной точки иммунного ответа с миметиком ограничения калорийности для лечения рака |
| JP7417804B2 (ja) | 2018-03-14 | 2024-01-19 | オーリジーン オンコロジー リミテッド | 1,2,4-オキサジアゾール化合物を用いてtigitおよびpd-1のシグナル伝達経路をモジュレートする方法 |
| EP3765517A1 (en) | 2018-03-14 | 2021-01-20 | Elstar Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
| EP3765516A2 (en) | 2018-03-14 | 2021-01-20 | Elstar Therapeutics, Inc. | Multifunctional molecules and uses thereof |
| 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 |
| BR112020018709A2 (pt) | 2018-03-28 | 2021-01-05 | Bristol-Myers Squibb Company | Proteínas de fusão do receptor alfa de interleucina-2/interleucina-2 e métodos de uso |
| WO2019185792A1 (en) | 2018-03-29 | 2019-10-03 | Philogen S.P.A | Cancer treatment using immunoconjugates and immune check-point inhibitors |
| KR20200142542A (ko) | 2018-04-12 | 2020-12-22 | 브리스톨-마이어스 스큅 컴퍼니 | Cd73 길항제 항체 및 pd-1/pd-l1 축 길항제 항체에 의한 항암 조합 요법 |
| KR20210010862A (ko) | 2018-04-18 | 2021-01-28 | 젠코어 인코포레이티드 | IL-15/IL-15Rα Fc-융합 단백질 및 PD-1 항원 결합 도메인을 함유하는 PD-1 표적화 이종이량체 융합 단백질 및 이의 용도 |
| MA52289A (fr) | 2018-04-18 | 2021-02-24 | Xencor Inc | Protéines de fusion fc hétérodimères il-15/il-15ra et leurs utilisations |
| US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
| US20210386829A1 (en) | 2018-05-04 | 2021-12-16 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses |
| KR102813281B1 (ko) | 2018-05-23 | 2025-05-28 | 셀진 코포레이션 | 병용 사용을 위한 bcma 및 cd3에 대한 항증식성 화합물 및 이중특이성 항체 |
| KR102718800B1 (ko) | 2018-05-23 | 2024-10-18 | 셀진 코포레이션 | 다발성 골수종의 치료 및 4-(4-(4-(((2-(2,6-디옥소피페리딘-3-일)-1-옥소이소인돌린-4-일)옥시)메틸)벤질)피페라진-1-일)-3-플루오로벤조니트릴에 대한 바이오마커의 용도 |
| US12331068B2 (en) | 2018-05-31 | 2025-06-17 | Peloton Therapeutics, Inc. | Compositions and methods for inhibiting CD73 |
| AU2019276656A1 (en) | 2018-06-01 | 2021-01-07 | Novartis Ag | Dosing of a bispecific antibody that bind CD123 and CD3 |
| WO2019232542A2 (en) | 2018-06-01 | 2019-12-05 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
| EP3818083A2 (en) | 2018-07-03 | 2021-05-12 | Elstar Therapeutics, Inc. | Anti-tcr antibody molecules and uses thereof |
| US20210236633A1 (en) | 2018-08-06 | 2021-08-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers |
| EP3617230A1 (en) | 2018-09-03 | 2020-03-04 | BioInvent International AB | Novel antibodies and nucleotide sequences, and uses thereof |
| WO2020048942A1 (en) | 2018-09-04 | 2020-03-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for enhancing cytotoxic t lymphocyte-dependent immune responses |
| JP7654539B2 (ja) | 2018-09-07 | 2025-04-01 | ファイザー・インク | 抗αvβ8抗体、組成物及びその使用 |
| US20220073638A1 (en) | 2018-09-19 | 2022-03-10 | INSERM (Institut National de la Santé et de la Recherche Médicale | Methods and pharmaceutical composition for the treatment of cancers resistant to immune checkpoint therapy |
| WO2020061482A1 (en) | 2018-09-21 | 2020-03-26 | Harpoon Therapeutics, Inc. | Egfr binding proteins and methods of use |
| AU2019346466A1 (en) | 2018-09-25 | 2021-05-20 | Harpoon Therapeutics, Inc. | DLL3 binding proteins and methods of use |
| JP7465272B2 (ja) | 2018-09-27 | 2024-04-10 | マレンゴ・セラピューティクス,インコーポレーテッド | Csf1r/ccr2多特異性抗体 |
| EP3860578A1 (en) | 2018-10-01 | 2021-08-11 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Use of inhibitors of stress granule formation for targeting the regulation of immune responses |
| JP7612571B2 (ja) | 2018-10-03 | 2025-01-14 | ゼンコア インコーポレイテッド | Il-12ヘテロ二量体fc-融合タンパク質 |
| WO2020077236A1 (en) | 2018-10-12 | 2020-04-16 | The Broad Institute, Inc. | Method for extracting nuclei or whole cells from formalin-fixed paraffin-embedded tissues |
| CR20210239A (es) | 2018-10-12 | 2021-12-15 | Xencor Inc | Proteínas de fusión de il-15/il-15ralfa-fc dirigidas a pd-1 y usos de las mismas en terapias combinadas |
| US20210379057A1 (en) | 2018-10-16 | 2021-12-09 | Massachusetts Institute Of Technology | Nutlin-3a for use in treating a mycobacterium tuberculosis infection |
| EP3867269A1 (en) | 2018-10-18 | 2021-08-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Combination of a big-h3 antagonist and an immune checkpoint inhibitor for the treatment of solid tumor |
| MX2021004906A (es) | 2018-10-29 | 2021-09-10 | Mersana Therapeutics Inc | Conjugados de anticuerpo modificado con cisteína-fármaco con enlazadores que contienen péptidos. |
| JP2022512973A (ja) | 2018-11-09 | 2022-02-07 | ピエリアン バイオサイエンシーズ リミテッド ライアビリティ カンパニー | 腫瘍微小環境の組成を測定するための方法及び組成物 |
| US12165743B2 (en) | 2018-11-09 | 2024-12-10 | The Broad Institute, Inc. | Compressed sensing for screening and tissue imaging |
| US12402610B2 (en) | 2018-11-09 | 2025-09-02 | The Broad Institute, Inc. | Methods and compositions for modulating innate lymphoid cell pathogenic effectors |
| SG11202104337PA (en) | 2018-11-26 | 2021-05-28 | Massachusetts Inst Technology | Compositions and methods for immune tolerance |
| EP3887823B1 (en) | 2018-11-28 | 2024-01-17 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and kit for assaying lytic potential of immune effector cells |
| AU2019392090A1 (en) | 2018-12-03 | 2021-06-17 | Agensys, Inc. | Pharmaceutical compositions comprising anti-191P4D12 antibody drug conjugates and methods of use thereof |
| WO2020115262A1 (en) | 2018-12-07 | 2020-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of cd26 and cd39 as new phenotypic markers for assessing maturation of foxp3+ t cells and uses thereof for diagnostic purposes |
| MA54448A (fr) | 2018-12-11 | 2021-10-20 | Theravance Biopharma R&D Ip Llc | Dérivés naphthyridine et quinoléine en tant qu'inhibiteurs de alk5 |
| US20220047556A1 (en) | 2018-12-17 | 2022-02-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sulconazole as a furin inhibitor |
| WO2020132646A1 (en) | 2018-12-20 | 2020-06-25 | Xencor, Inc. | Targeted heterodimeric fc fusion proteins containing il-15/il-15ra and nkg2d antigen binding domains |
| WO2020140012A1 (en) | 2018-12-27 | 2020-07-02 | Amgen Inc. | Lyophilized virus formulations |
| MX2021007860A (es) | 2018-12-28 | 2021-10-26 | Transgene | Poxvirux deficiente en m2. |
| BR112021013157A8 (pt) | 2019-01-03 | 2022-12-06 | Inst Nat Sante Rech Med | Usos de um inibidor de nrp-1, uso de uma combinação, uso de um anticorpo multiespecífico, método ex vivo para predizer, uso de um inibidor, anticorpo multiespecífico, população de células modificadas, método ex vivo de produção e uso de uma população de células t |
| US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
| AU2020206694B2 (en) | 2019-01-09 | 2025-05-22 | Celgene Corporation | Solid forms comprising (S)-4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl) benzyl)piperazin-1-yl)-3-fluorobenzonitrile and salts thereof, and compositions comprising and methods of using the same |
| CN114409630B (zh) | 2019-01-09 | 2024-04-02 | 细胞基因公司 | 包含氧代异吲哚化合物的药物组合物以及使用它的方法 |
| EA202191903A1 (ru) | 2019-01-09 | 2021-11-12 | Селджин Корпорейшн | Антипролиферативные соединения и вторые активные агенты для комбинированного применения |
| ES3011707T3 (en) | 2019-01-15 | 2025-04-08 | Inst Nat Sante Rech Med | Mutated interleukin-34 (il-34) polypeptides and uses thereof in therapy |
| WO2020169472A2 (en) | 2019-02-18 | 2020-08-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of inducing phenotypic changes in macrophages |
| WO2020172343A2 (en) | 2019-02-19 | 2020-08-27 | Massachusetts Institute Of Technology | Methods for treating injuries |
| CN119661722A (zh) | 2019-02-21 | 2025-03-21 | 马伦戈治疗公司 | 结合t细胞相关癌细胞的多功能分子及其用途 |
| SG11202108955QA (en) | 2019-02-21 | 2021-09-29 | Marengo Therapeutics Inc | Antibody molecules that bind to nkp30 and uses thereof |
| BR112021017551A2 (pt) | 2019-03-05 | 2021-11-09 | Amgen Inc | Uso de vírus oncolíticos para o tratamento de câncer |
| US20220154282A1 (en) | 2019-03-12 | 2022-05-19 | The Broad Institute, Inc. | Detection means, compositions and methods for modulating synovial sarcoma cells |
| WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
| WO2020186235A1 (en) | 2019-03-14 | 2020-09-17 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate intestinal innate lymphoid cells |
| US20220152148A1 (en) | 2019-03-18 | 2022-05-19 | The Broad Institute, Inc. | Modulation of type 2 immunity by targeting clec-2 signaling |
| EP3942023A1 (en) | 2019-03-18 | 2022-01-26 | The Broad Institute, Inc. | Compositions and methods for modulating metabolic regulators of t cell pathogenicity |
| TW202102543A (zh) | 2019-03-29 | 2021-01-16 | 美商安進公司 | 溶瘤病毒在癌症新輔助療法中之用途 |
| CN114126637A (zh) | 2019-03-29 | 2022-03-01 | 居里研究所 | 具有经修饰的生物活性的白介素-2变体 |
| EP3947640A4 (en) | 2019-04-02 | 2022-12-14 | The Brigham & Women's Hospital, Inc. | PROCEDURE FOR DETERMINING THE PROGRESSION OF PRIMARY MELANOMA |
| US20220177978A1 (en) | 2019-04-02 | 2022-06-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of predicting and preventing cancer in patients having premalignant lesions |
| WO2020208060A1 (en) | 2019-04-09 | 2020-10-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk2 inhibitors in combination with immune checkpoint blockade therapy for the treatment of cancer |
| WO2020212484A1 (en) | 2019-04-17 | 2020-10-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treatment of nlrp3 inflammasome mediated il-1beta dependent disorders |
| US12404331B2 (en) | 2019-04-19 | 2025-09-02 | Tcrcure Biopharma Corp. | Anti-PD-1 antibodies and uses thereof |
| WO2020236253A1 (en) | 2019-05-20 | 2020-11-26 | Massachusetts Institute Of Technology | Boronic ester prodrugs and uses thereof |
| WO2020243371A1 (en) | 2019-05-28 | 2020-12-03 | Massachusetts Institute Of Technology | Methods and compositions for modulating immune responses |
| WO2020243661A1 (en) | 2019-05-31 | 2020-12-03 | The Broad Institute, Inc. | Methods for treating metabolic disorders by targeting adcy5 |
| US11246906B2 (en) | 2019-06-11 | 2022-02-15 | Alkermes Pharma Ireland Limited | Compositions and methods for subcutaneous administration of cancer immunotherapy |
| BR112021026832A2 (pt) | 2019-07-02 | 2022-05-10 | Hutchinson Fred Cancer Res | Vetores ad35 recombinantes e aprimoramentos da terapia gênica relacionada |
| WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
| CA3149494A1 (en) | 2019-08-12 | 2021-02-18 | Purinomia Biotech, Inc. | Methods and compositions for promoting and potentiating t-cell mediated immune responses through adcc targeting of cd39 expressing cells |
| WO2021030627A1 (en) | 2019-08-13 | 2021-02-18 | The General Hospital Corporation | Methods for predicting outcomes of checkpoint inhibition and treatment thereof |
| US12421557B2 (en) | 2019-08-16 | 2025-09-23 | The Broad Institute, Inc. | Methods for predicting outcomes and treating colorectal cancer using a cell atlas |
| US20220411388A1 (en) | 2019-09-17 | 2022-12-29 | Bial - R&D Investments, S.A. | Substituted imidazole carboxamides and their use in the treatment of medical disorders |
| JP2022549227A (ja) | 2019-09-17 | 2022-11-24 | バイアル-アールアンドディー インベストメンツ ソシエダッド アノニマ | 医学的障害の治療における使用のための置換された飽和および不飽和n-複素環式カルボキサミドおよび関連化合物 |
| AU2020349519A1 (en) | 2019-09-17 | 2022-03-17 | Bial-R&D Investments, S.A. | Substituted N-heterocyclic carboxamides as acid ceramidase inhibitors and their use as medicaments |
| US20220347294A1 (en) | 2019-09-23 | 2022-11-03 | The Regents Of The University Of Michigan | Compositions and methods for increasing the efficacy of immunotherapies and vaccines |
| EP3800201A1 (en) | 2019-10-01 | 2021-04-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cd28h stimulation enhances nk cell killing activities |
| US12195725B2 (en) | 2019-10-03 | 2025-01-14 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating and detecting tissue specific TH17 cell pathogenicity |
| AU2020358979A1 (en) | 2019-10-03 | 2022-04-21 | Xencor, Inc. | Targeted IL-12 heterodimeric Fc-fusion proteins |
| US11981922B2 (en) | 2019-10-03 | 2024-05-14 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment |
| WO2021067521A1 (en) | 2019-10-04 | 2021-04-08 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| EP4037710A1 (en) | 2019-10-04 | 2022-08-10 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and pharmaceutical composition for the treatment of ovarian cancer, breast cancer or pancreatic cancer |
| US11793787B2 (en) | 2019-10-07 | 2023-10-24 | The Broad Institute, Inc. | Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis |
| TW202128757A (zh) | 2019-10-11 | 2021-08-01 | 美商建南德克公司 | 具有改善之特性的 PD-1 標靶 IL-15/IL-15Rα FC 融合蛋白 |
| US20220401539A1 (en) | 2019-10-22 | 2022-12-22 | Institut Curie | Immunotherapy Targeting Tumor Neoantigenic Peptides |
| JP2022554346A (ja) | 2019-11-05 | 2022-12-28 | セルジーン コーポレーション | 2-(4-クロロフェニル)-n-((2-(2,6-ジオキソピペリジン-3-イル)-1-オキソイソインドリン-5-イル)メチル)-2,2-ジフルオロアセトアミドとの併用療法 |
| EP3824954A1 (en) | 2019-11-22 | 2021-05-26 | Centre National de la Recherche Scientifique | Device, apparatus and method for minibeam radiation therapy |
| CA3160307A1 (en) | 2019-11-22 | 2021-05-27 | Theravance Biopharma R&D Ip, Llc | Substituted 1,5-naphthyridines or quinolines as alk5 inhibitors |
| US11865168B2 (en) | 2019-12-30 | 2024-01-09 | Massachusetts Institute Of Technology | Compositions and methods for treating bacterial infections |
| WO2021138407A2 (en) | 2020-01-03 | 2021-07-08 | Marengo Therapeutics, Inc. | Multifunctional molecules that bind to cd33 and uses thereof |
| GB2609554B (en) | 2020-01-03 | 2025-08-20 | Marengo Therapeutics Inc | Anti-TCR antibody molecules and uses thereof |
| IL272194A (en) | 2020-01-22 | 2021-07-29 | Yeda Res & Dev | Multi-target antibodies for use in the treatment of diseases |
| US12165747B2 (en) | 2020-01-23 | 2024-12-10 | The Broad Institute, Inc. | Molecular spatial mapping of metastatic tumor microenvironment |
| TW202146452A (zh) | 2020-02-28 | 2021-12-16 | 瑞士商諾華公司 | 結合cd123和cd3之雙特異性抗體的給藥 |
| WO2021183428A1 (en) | 2020-03-09 | 2021-09-16 | Bristol-Myers Squibb Company | Antibodies to cd40 with enhanced agonist activity |
| WO2021183318A2 (en) | 2020-03-09 | 2021-09-16 | President And Fellows Of Harvard College | Methods and compositions relating to improved combination therapies |
| WO2021203131A1 (en) | 2020-03-31 | 2021-10-07 | Theravance Biopharma R&D Ip, Llc | Substituted pyrimidines and methods of use |
| EP4139341A1 (en) | 2020-04-21 | 2023-03-01 | Regeneron Pharmaceuticals, Inc. | Il-2 variants with reduced binding to il-2 receptor alpha and uses thereof |
| CA3175499A1 (en) | 2020-04-21 | 2021-10-28 | University Of Rochester | Inhibitors of human epididymus protein 4 |
| KR20230037069A (ko) | 2020-04-22 | 2023-03-15 | 이오반스 바이오테라퓨틱스, 인크. | 환자-특이적 면역요법을 위해 세포의 제조를 조정하기 위한 시스템 및 방법 |
| WO2021224186A1 (en) | 2020-05-04 | 2021-11-11 | Institut Curie | New pyridine derivatives as radiosensitizers |
| WO2021231732A1 (en) | 2020-05-15 | 2021-11-18 | Bristol-Myers Squibb Company | Antibodies to garp |
| CN115968377A (zh) | 2020-05-20 | 2023-04-14 | 居里研究所 | 单域抗体及其在癌症治疗中的用途 |
| WO2021242794A2 (en) | 2020-05-29 | 2021-12-02 | President And Fellows Of Harvard College | Living cells engineered with polyphenol-functionalized biologically active nanocomplexes |
| JP2023528071A (ja) | 2020-06-03 | 2023-07-03 | エムヴィ バイオセラピューティクス エスエー | Atp加水分解酵素と免疫チェックポイントモジュレーターとの組合せ、並びにその使用 |
| TW202214623A (zh) | 2020-06-10 | 2022-04-16 | 美商施萬生物製藥研發 Ip有限責任公司 | 結晶型alk5抑制劑及其用途 |
| WO2021260675A1 (en) | 2020-06-24 | 2021-12-30 | Yeda Research And Development Co. Ltd. | Agents for sensitizing solid tumors to treatment |
| AU2021296876A1 (en) | 2020-06-25 | 2023-02-02 | Celgene Corporation | Methods for treating cancer with combination therapies |
| CN115843335A (zh) | 2020-06-30 | 2023-03-24 | 国家医疗保健研究所 | 用于预测患有实体癌的患者在术前辅助治疗和根治性手术后复发和/或死亡风险的方法 |
| CN115997123A (zh) | 2020-06-30 | 2023-04-21 | 国家医疗保健研究所 | 用于预测实体癌患者在术前辅助治疗后复发和/或死亡风险的方法 |
| WO2022003156A1 (en) | 2020-07-02 | 2022-01-06 | Oncurious Nv | Ccr8 non-blocking binders |
| KR20230035598A (ko) | 2020-07-07 | 2023-03-14 | 셀진 코포레이션 | (s)-4-(4-(4-(((2-(2,6-디옥소피페리딘-3-일)-1-옥소이소인돌린-4-일)옥시)메틸)벤질)피페라진-1-일)-3-플루오로벤조니트릴을 포함하는 약제학적 조성물 및 이를 사용하는 방법 |
| AU2021305084A1 (en) | 2020-07-07 | 2023-02-02 | Cancure, Llc | MIC antibodies and binding agents and methods of using the same |
| AU2021306613A1 (en) | 2020-07-07 | 2023-02-02 | BioNTech SE | Therapeutic RNA for HPV-positive cancer |
| US20230295146A1 (en) | 2020-07-24 | 2023-09-21 | The University Of Rochester | Inhibitors of interleukin-1 receptor-associated kinases 1 and 4 |
| CN116194138A (zh) | 2020-08-07 | 2023-05-30 | 博德研究所 | 治疗性靶向癌症中经由xpr1:kidins220蛋白质复合物的磷酸盐调节异常 |
| WO2022047046A1 (en) | 2020-08-26 | 2022-03-03 | Marengo Therapeutics, Inc. | Methods of detecting trbc1 or trbc2 |
| EP4229090A1 (en) | 2020-10-16 | 2023-08-23 | Université d'Aix-Marseille | Anti-gpc4 single domain antibodies |
| EP4232453A1 (en) | 2020-10-20 | 2023-08-30 | Institut Curie | Metallic trans-(n-heterocyclic carbene)-amine-platinum complexes and uses thereof for treating cancer |
| KR20230104659A (ko) | 2020-11-08 | 2023-07-10 | 씨젠 인크. | 면역 세포 억제제를 이용한 조합-요법 항체 약물 접합체 |
| JP2023550402A (ja) | 2020-11-18 | 2023-12-01 | アンスティテュ・クリー | ビグアニジンの二量体及びその治療的使用 |
| WO2022130206A1 (en) | 2020-12-16 | 2022-06-23 | Pfizer Inc. | TGFβr1 INHIBITOR COMBINATION THERAPIES |
| WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
| WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
| TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性rna |
| WO2022136649A1 (en) | 2020-12-24 | 2022-06-30 | Oncurious Nv | Non-blocking human ccr8 binders |
| WO2022136647A1 (en) | 2020-12-24 | 2022-06-30 | Oncurious Nv | Human ccr8 binders |
| EP4267621A1 (en) | 2020-12-24 | 2023-11-01 | Vib Vzw | Murine cross-reactive human ccr8 binders |
| CN117916271A (zh) | 2021-01-14 | 2024-04-19 | 居里研究所 | Her2单域抗体变体及其car |
| WO2022189618A1 (en) | 2021-03-12 | 2022-09-15 | Institut Curie | Nitrogen-containing heterocycles as radiosensitizers |
| WO2022212876A1 (en) | 2021-04-02 | 2022-10-06 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
| EP4320147A4 (en) | 2021-04-08 | 2025-06-18 | Marengo Therapeutics, Inc. | TCR-BINDING MULTIFUNCTIONAL MOLECULES AND USES THEREOF |
| TW202304524A (zh) | 2021-04-10 | 2023-02-01 | 美商普方生物製藥美國公司 | Folr1結合劑、其結合物及使用方法 |
| AU2022262644A1 (en) | 2021-04-23 | 2023-11-09 | Genmab A/S | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
| WO2022235754A1 (en) | 2021-05-05 | 2022-11-10 | Bristol-Myers Squibb Company | Lactone and lactam containing compounds useful as immunomodulators |
| WO2022238386A1 (en) | 2021-05-10 | 2022-11-17 | Institut Curie | Methods for the treatment of cancer, inflammatory diseases and autoimmune diseases |
| WO2022251359A1 (en) | 2021-05-26 | 2022-12-01 | Theravance Biopharma R&D Ip, Llc | Bicyclic inhibitors of alk5 and methods of use |
| BR112023022097A2 (pt) | 2021-06-07 | 2023-12-19 | Agonox Inc | Cxcr5, pd-1 e icos expressando células t cd4 reativas de tumor e seu uso |
| EP4352077A1 (en) | 2021-06-09 | 2024-04-17 | Bristol-Myers Squibb Company | Cyclic peptide immunomodulators |
| US20240316005A1 (en) | 2021-07-05 | 2024-09-26 | Institut National de la Santé et de la Recherche Médicale | Gene signatures for predicting survival time in patients suffering from renal cell carcinoma |
| US20250230153A1 (en) | 2021-07-06 | 2025-07-17 | Bristol-Myers Squibb Company | 2,3-dihydrobenzo[b][1,4]dioxin-6-yl containing compounds useful as immunomodulators |
| JP2024525758A (ja) | 2021-07-13 | 2024-07-12 | ビオンテック・ソシエタス・エウロパエア | がんのための併用療法におけるcd40およびcd137に対する多重特異性結合剤 |
| WO2023011879A1 (en) | 2021-08-05 | 2023-02-09 | Institut Curie | Scanning dynamic device for minibeams production |
| AU2022332285A1 (en) | 2021-08-23 | 2024-02-15 | Immunitas Therapeutics, Inc. | Anti-cd161 antibodies and uses thereof |
| EP4401715A1 (en) | 2021-09-17 | 2024-07-24 | Institut Curie | Bet inhibitors for treating pab1 deficient cancer |
| TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
| JP2024540536A (ja) | 2021-11-19 | 2024-10-31 | アーディアジェン コーポレーション | Gpc3結合剤、そのコンジュゲートおよびその使用方法 |
| EP4433089A1 (en) | 2021-11-19 | 2024-09-25 | Institut Curie | Methods for the treatment of hrd cancer and brca-associated cancer |
| WO2023099763A1 (en) | 2021-12-03 | 2023-06-08 | Institut Curie | Sirt6 inhibitors for use in treating resistant hrd cancer |
| EP4453034A1 (en) | 2021-12-23 | 2024-10-30 | The Broad Institute Inc. | Parallel antibody engineering compositions and methods |
| WO2023154799A1 (en) | 2022-02-14 | 2023-08-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Combination immunotherapy for treating cancer |
| AU2023230110A1 (en) | 2022-03-08 | 2024-10-24 | Alentis Therapeutics Ag | Use of anti-claudin-1 antibodies to increase t cell availability |
| EP4499134A1 (en) | 2022-03-24 | 2025-02-05 | Institut Curie | Immunotherapy targeting tumor transposable element derived neoantigenic peptides in glioblastoma |
| EP4499677A1 (en) | 2022-03-31 | 2025-02-05 | Institut Curie | Modified rela protein for inducing interferon expression and engineered immune cells with improved interferon expression |
| US20250241949A1 (en) | 2022-04-07 | 2025-07-31 | Institut Curie | Myeloid cells modified by chimeric antigen receptor and uses thereof for anti-cancer therapy |
| US20250222106A1 (en) | 2022-04-07 | 2025-07-10 | Institut Curie | Myeloid cells modified by chimeric antigen receptor with cd40 and uses thereof for anti-cancer therapy |
| EP4507704A1 (en) | 2022-04-15 | 2025-02-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
| WO2023213763A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Poxvirus encoding a binding agent comprising an anti- pd-l1 sdab |
| WO2023213764A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Fusion polypeptide comprising an anti-pd-l1 sdab and a member of the tnfsf |
| JP2025523573A (ja) | 2022-07-01 | 2025-07-23 | トランジェーヌ | サーファクタントタンパク質-dとtnfsfのメンバーを含んでなる融合タンパク質 |
| CN120225541A (zh) | 2022-07-14 | 2025-06-27 | 博德研究所 | 通过与转铁蛋白受体的相互作用实现cns范围的基因递送的aav衣壳 |
| EP4583860A1 (en) | 2022-09-06 | 2025-07-16 | Institut National de la Santé et de la Recherche Médicale | Inhibitors of the ceramide metabolic pathway for overcoming immunotherapy resistance in cancer |
| JP2025532209A (ja) | 2022-09-26 | 2025-09-29 | アンスティテュ・クリー | Il-2を発現する骨髄系細胞及び迅速な抗癌療法のためのその使用 |
| EP4605422A2 (en) | 2022-10-20 | 2025-08-27 | Repertoire Immune Medicines, Inc. | Cd8 t cell targeted il2 |
| JP2025536252A (ja) | 2022-10-20 | 2025-11-05 | アンセルム(アンスティチュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル) | 癌治療のための併用療法 |
| EP4608390A1 (en) | 2022-10-24 | 2025-09-03 | Cancer Research Technology Limited | Tumour sensitisation to checkpoint inhibitors with redox status modifier |
| WO2024089417A1 (en) | 2022-10-24 | 2024-05-02 | Memorial Sloan-Kettering Cancer Center | Tumour stratification for responsiveness to an immune checkpoint inhibitor |
| EP4623072A2 (en) | 2022-11-21 | 2025-10-01 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
| KR20250120305A (ko) | 2022-12-14 | 2025-08-08 | 아스텔라스 파마 유럽 비.브이. | Cldn18.2 및 cd3에 결합하는 2중 특이성 결합제와 면역 체크포인트 저해제를 수반한 조합 요법 |
| EP4658687A1 (en) | 2023-01-31 | 2025-12-10 | University of Rochester | Immune checkpoint blockade therapy for treating staphylococcus aureus infections |
| WO2024192141A1 (en) | 2023-03-13 | 2024-09-19 | Dana-Farber Cancer Institute, Inc. | Treatment of cancers having a drug-resistant mesenchymal cell state |
| WO2024194673A1 (en) | 2023-03-21 | 2024-09-26 | Institut Curie | Methods for the treatment of dedifferentiated liposarcoma |
| WO2024194402A1 (en) | 2023-03-21 | 2024-09-26 | Institut Curie | Farnesyl transferase inhibitor for use in methods for the treatment of hrd cancer |
| WO2024194401A1 (en) | 2023-03-21 | 2024-09-26 | Institut Curie | Vps4b inhibitor for use in methods for the treatment of hrd cancer |
| WO2024213782A1 (en) | 2023-04-13 | 2024-10-17 | Institut Curie | Methods for the treatment of t-cell acute lymphoblastic leukemia |
| WO2024213767A1 (en) | 2023-04-14 | 2024-10-17 | Institut National de la Santé et de la Recherche Médicale | Engraftment of mesenchymal stromal cells engineered to stimulate immune infiltration in tumors |
| WO2024261302A1 (en) | 2023-06-22 | 2024-12-26 | Institut National de la Santé et de la Recherche Médicale | Nlrp3 inhibitors, pak1/2 inhibitors and/or caspase 1 inhibitors for use in the treatment of rac2 monogenic disorders |
| WO2025003193A1 (en) | 2023-06-26 | 2025-01-02 | Institut National de la Santé et de la Recherche Médicale | Sertraline and indatraline for disrupting intracellular cholesterol trafficking and subsequently inducing lysosomal damage and anti-tumor immunity |
| WO2025012417A1 (en) | 2023-07-13 | 2025-01-16 | Institut National de la Santé et de la Recherche Médicale | Anti-neurotensin long fragment and anti-neuromedin n long fragment antibodies and uses thereof |
| US20250051434A1 (en) | 2023-08-11 | 2025-02-13 | Merck Sharp & Dohme Llc | Monovalent interleukin 12 (il-12) heterodimeric fc proteins |
| WO2025068393A1 (en) | 2023-09-27 | 2025-04-03 | Institut Curie | Methods for the treatment of fibrotic related diseases |
| WO2025120866A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| WO2025121445A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| WO2025120867A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and anti-vegfr2 antibodies |
| WO2025133175A1 (en) | 2023-12-21 | 2025-06-26 | Egle Therapeutics | Immunocytokine for cancer treatment |
| EP4574165A1 (en) | 2023-12-21 | 2025-06-25 | Egle Therapeutics | Immunocytokine for cancer treatment |
| WO2025155923A1 (en) | 2024-01-17 | 2025-07-24 | The Broad Institute, Inc. | Aav capsid modifications that enable improved cns-wide gene delivery through interactions with the transferrin receptor |
| WO2025158077A1 (en) | 2024-01-26 | 2025-07-31 | Institut Curie | Lipid degraders to trigger ferroptosis in cancer |
| WO2025163468A1 (en) | 2024-01-30 | 2025-08-07 | Seagen Inc. | Anti-pd-l1 antibodies and antibody-drug conjugates and their use in the treatment of cancer |
| WO2025202222A1 (en) | 2024-03-25 | 2025-10-02 | Institut National de la Santé et de la Recherche Médicale | Therapeutic use of sting and tlrs agonists to induce p16 expression in immune cells |
| WO2025202213A1 (en) | 2024-03-26 | 2025-10-02 | Institut National de la Santé et de la Recherche Médicale | Lipid nanoparticle loaded with antitumoral agent and functionnalized to target immosuppressive cells |
| WO2025202450A1 (en) | 2024-03-28 | 2025-10-02 | Institut Curie | Myeloid cells modified by cytokine chimeric receptor and uses thereof |
| EP4624494A1 (en) | 2024-03-29 | 2025-10-01 | Institut Curie | Her2 single domain antibody and uses thereof |
| WO2025210175A1 (en) | 2024-04-04 | 2025-10-09 | Centre National De La Recherche Scientifique | Mutant csf-1r extracellular domain fusion molecules and therapeutic uses thereof |
| WO2025210252A1 (en) | 2024-04-05 | 2025-10-09 | Institut Curie | Modulators of fam118b protein for use in therapy |
| WO2025217096A1 (en) | 2024-04-08 | 2025-10-16 | University Of Rochester | Inhibitors of leucine-rich repeat kinase 2 (lrrk2) and medical uses thereof |
| WO2025217163A2 (en) | 2024-04-08 | 2025-10-16 | The Broad Institute, Inc. | Novel aav capsids binding to human cd59 |
| WO2025217174A1 (en) | 2024-04-08 | 2025-10-16 | The Broad Institute, Inc. | Aav capsid modifications that enable improved cns-wide gene delivery through interactions with carbonic anhydrase iv |
| WO2025217094A1 (en) | 2024-04-08 | 2025-10-16 | University Of Rochester | Interleukin receptor-associated kinase (irak) protac degraders and medical use thereof |
| WO2025219595A1 (en) | 2024-04-19 | 2025-10-23 | Biper Therapeutics | Method for combination treatments using alkynylbenzenesulphonamides for cancer therapy |
| WO2025232879A1 (en) | 2024-05-10 | 2025-11-13 | Cytocares (Shanghai) Inc. | Anti-lilrb2 monospecific and bispecific antibody constructs and uses thereof |
| GB202408360D0 (en) | 2024-06-11 | 2024-07-24 | Cancer Research Tech Ltd | Tumour sensitisation |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US556763A (en) * | 1896-03-24 | Telephone-switch | ||
| US6090914A (en) * | 1991-06-27 | 2000-07-18 | Bristol-Myers Squibb Company | CTLA4/CD28Ig hybrid fusion proteins and uses thereof |
| AU661854B2 (en) * | 1991-06-27 | 1995-08-10 | Bristol-Myers Squibb Company | CTL4A receptor, fusion proteins containing it and uses thereof |
| US5770197A (en) * | 1991-06-27 | 1998-06-23 | Bristol-Myers Squibb Company | Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules |
| US5556763A (en) * | 1992-04-06 | 1996-09-17 | United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Evaluation and treatment of patients with progressive immunosuppression |
| EP0665852A1 (en) * | 1993-07-09 | 1995-08-09 | Amgen Boulder Inc. | Recombinant ctla4 polypeptides and methods for making the same |
| EP0711345A1 (en) * | 1993-07-26 | 1996-05-15 | Dana Farber Cancer Institute | B7-2: ctl a4/cd 28 counter receptor |
| AU7526894A (en) * | 1993-08-16 | 1995-03-14 | Arch Development Corporation | B7-2: ctla4/cd28 counter receptor |
| US6218510B1 (en) * | 1994-03-02 | 2001-04-17 | Brigham & Woman's Hospital | B7-1 and B7-2 polypeptides |
| EP1025856A3 (en) * | 1994-03-08 | 2002-10-16 | Dana-Farber Cancer Institute | Methods for modulating T Cell unresponsiveness |
| US6719972B1 (en) * | 1994-06-03 | 2004-04-13 | Repligen Corporation | Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA4- specific antibodies |
| EP0784482A2 (en) * | 1994-06-07 | 1997-07-23 | The Regents Of The University Of Minnesota | Methods for inhibiting antigen specific t cell responses |
| AU4158396A (en) * | 1994-11-10 | 1996-06-06 | Dana-Farber Cancer Institute | Methods for inhibiting graft versus host disease in bone marrow transplantation |
-
1996
- 1996-05-08 US US08/646,605 patent/US5811097A/en not_active Expired - Lifetime
- 1996-12-04 WO PCT/US1996/019375 patent/WO1997020574A1/en not_active Ceased
- 1996-12-04 EP EP96942901A patent/EP0865293B1/en not_active Revoked
- 1996-12-04 CA CA2239448A patent/CA2239448C/en not_active Expired - Lifetime
- 1996-12-04 DK DK96942901T patent/DK0865293T3/da active
- 1996-12-04 EP EP10180032.4A patent/EP2332561B1/en not_active Expired - Lifetime
- 1996-12-04 ES ES96942901T patent/ES2318853T3/es not_active Expired - Lifetime
- 1996-12-04 AU AU11473/97A patent/AU730500B2/en not_active Expired
- 1996-12-04 PT PT96942901T patent/PT865293E/pt unknown
- 1996-12-04 CA CA2770851A patent/CA2770851C/en not_active Expired - Lifetime
- 1996-12-04 DK DK10180032.4T patent/DK2332561T3/en active
- 1996-12-04 DE DE69637762T patent/DE69637762D1/de not_active Expired - Fee Related
- 1996-12-04 ES ES10180032.4T patent/ES2579277T3/es not_active Expired - Lifetime
- 1996-12-04 EP EP08020208.8A patent/EP2106800B1/en not_active Expired - Lifetime
- 1996-12-04 JP JP52142597A patent/JP4477701B2/ja not_active Expired - Lifetime
- 1996-12-04 AT AT96942901T patent/ATE415172T1/de active
- 1996-12-04 PT PT101800324T patent/PT2332561E/pt unknown
-
2008
- 2008-11-13 JP JP2008291542A patent/JP2009114191A/ja not_active Withdrawn
-
2012
- 2012-01-05 DE DE201212000002 patent/DE122012000002I1/de active Pending
- 2012-01-09 LU LU91927C patent/LU91927I2/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0865293A4 (en) | 2002-02-06 |
| JP4477701B2 (ja) | 2010-06-09 |
| CA2770851A1 (en) | 1997-06-12 |
| EP2332561A1 (en) | 2011-06-15 |
| PT2332561E (pt) | 2016-06-14 |
| EP0865293A1 (en) | 1998-09-23 |
| JP2009114191A (ja) | 2009-05-28 |
| EP2106800A1 (en) | 2009-10-07 |
| LU91927I2 (fr) | 2012-03-09 |
| CA2770851C (en) | 2013-09-24 |
| EP2332561B1 (en) | 2016-03-30 |
| JP2000502331A (ja) | 2000-02-29 |
| US5811097A (en) | 1998-09-22 |
| ATE415172T1 (de) | 2008-12-15 |
| DE69637762D1 (de) | 2009-01-08 |
| DK0865293T3 (da) | 2009-03-23 |
| PT865293E (pt) | 2009-03-06 |
| DK2332561T3 (en) | 2016-06-06 |
| AU1147397A (en) | 1997-06-27 |
| EP2106800B1 (en) | 2016-12-07 |
| EP0865293B1 (en) | 2008-11-26 |
| ES2579277T3 (es) | 2016-08-09 |
| CA2239448A1 (en) | 1997-06-12 |
| ES2318853T3 (es) | 2009-05-01 |
| WO1997020574A1 (en) | 1997-06-12 |
| AU730500B2 (en) | 2001-03-08 |
| DE122012000002I1 (de) | 2012-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2239448C (en) | Blockade of t lymphocyte down-regulation associated with ctla-4 signaling | |
| US6051227A (en) | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling | |
| US5855887A (en) | Blockade of lymphocyte down-regulation associated with CTLA-4 signaling | |
| AU774962B2 (en) | Stimulation of T cells against self antigens using CTLA-4 blocking agents | |
| US6168923B1 (en) | Compositions and methods for use of IL-12 as an adjuvant | |
| US20090269353A1 (en) | Stimulation of T Cells Against Self-Antigens Using CTLA-4 Blocking Agents | |
| AU727652B2 (en) | Nerve growth factor as a vaccine adjuvant | |
| US5874085A (en) | Vaccine for enhanced production of IgA antibodies | |
| KR0183029B1 (ko) | 내성을 유도하기 위한 모노클론 항체류 | |
| KR20020001865A (ko) | 면역반응을 증강시키기 위한 가용성 공동자극 분자의 용도 | |
| DE69737456T2 (de) | Milcherzeugungsassoziiertes immunotropisches rinderprotein (cd14), kodierendes gen und verwendung zur aktivierung von b-zellen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20161205 |