JP2008515442A - B7−h1ならびに癌の診断、予後診断および処置の方法 - Google Patents
B7−h1ならびに癌の診断、予後診断および処置の方法 Download PDFInfo
- Publication number
- JP2008515442A JP2008515442A JP2007535894A JP2007535894A JP2008515442A JP 2008515442 A JP2008515442 A JP 2008515442A JP 2007535894 A JP2007535894 A JP 2007535894A JP 2007535894 A JP2007535894 A JP 2007535894A JP 2008515442 A JP2008515442 A JP 2008515442A
- Authority
- JP
- Japan
- Prior art keywords
- tissue
- cancer
- subject
- cells
- step comprises
- 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.)
- Granted
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 206
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 title claims abstract description 180
- 238000000034 method Methods 0.000 title claims abstract description 163
- 201000011510 cancer Diseases 0.000 title claims abstract description 116
- 238000011282 treatment Methods 0.000 title claims description 14
- 238000004393 prognosis Methods 0.000 title claims description 11
- 238000003745 diagnosis Methods 0.000 title claims description 5
- 238000012360 testing method Methods 0.000 claims abstract description 67
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 45
- 229920001184 polypeptide Polymers 0.000 claims abstract description 37
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 37
- 108020004999 messenger RNA Proteins 0.000 claims abstract description 27
- 230000003993 interaction Effects 0.000 claims abstract description 15
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 230000008901 benefit Effects 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims description 183
- 210000001519 tissue Anatomy 0.000 claims description 171
- 210000000265 leukocyte Anatomy 0.000 claims description 73
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 62
- 210000004881 tumor cell Anatomy 0.000 claims description 43
- 239000000523 sample Substances 0.000 claims description 41
- 108091030071 RNAI Proteins 0.000 claims description 31
- 239000003795 chemical substances by application Substances 0.000 claims description 31
- 230000009368 gene silencing by RNA Effects 0.000 claims description 31
- 108091034117 Oligonucleotide Proteins 0.000 claims description 27
- 239000012634 fragment Substances 0.000 claims description 25
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 19
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 19
- 238000009169 immunotherapy Methods 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 15
- 102000004127 Cytokines Human genes 0.000 claims description 14
- 108090000695 Cytokines Proteins 0.000 claims description 14
- 230000000692 anti-sense effect Effects 0.000 claims description 14
- 108010074328 Interferon-gamma Proteins 0.000 claims description 13
- 102000039446 nucleic acids Human genes 0.000 claims description 12
- 108020004707 nucleic acids Proteins 0.000 claims description 12
- 210000004072 lung Anatomy 0.000 claims description 10
- 210000000952 spleen Anatomy 0.000 claims description 10
- 210000000481 breast Anatomy 0.000 claims description 9
- 239000003102 growth factor Substances 0.000 claims description 9
- 125000003729 nucleotide group Chemical group 0.000 claims description 9
- 210000002784 stomach Anatomy 0.000 claims description 9
- 102000015696 Interleukins Human genes 0.000 claims description 8
- 108010063738 Interleukins Proteins 0.000 claims description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 8
- 210000000981 epithelium Anatomy 0.000 claims description 8
- 230000002452 interceptive effect Effects 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- 210000002307 prostate Anatomy 0.000 claims description 8
- 102000006992 Interferon-alpha Human genes 0.000 claims description 7
- 108010047761 Interferon-alpha Proteins 0.000 claims description 7
- 102000008070 Interferon-gamma Human genes 0.000 claims description 7
- 229960003130 interferon gamma Drugs 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 6
- 102100037850 Interferon gamma Human genes 0.000 claims description 6
- 108090000467 Interferon-beta Proteins 0.000 claims description 6
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 6
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 6
- 210000000232 gallbladder Anatomy 0.000 claims description 6
- 230000004957 immunoregulator effect Effects 0.000 claims description 6
- 210000005084 renal tissue Anatomy 0.000 claims description 6
- 210000001685 thyroid gland Anatomy 0.000 claims description 6
- 238000000684 flow cytometry Methods 0.000 claims description 5
- 210000003563 lymphoid tissue Anatomy 0.000 claims description 5
- 210000001550 testis Anatomy 0.000 claims description 5
- 210000001541 thymus gland Anatomy 0.000 claims description 5
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 4
- 108020004711 Nucleic Acid Probes Proteins 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 238000010240 RT-PCR analysis Methods 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 238000007901 in situ hybridization Methods 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims description 4
- 230000001537 neural effect Effects 0.000 claims description 4
- 239000002853 nucleic acid probe Substances 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 102400000068 Angiostatin Human genes 0.000 claims description 3
- 108010079709 Angiostatins Proteins 0.000 claims description 3
- 206010005949 Bone cancer Diseases 0.000 claims description 3
- 208000018084 Bone neoplasm Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 102400001047 Endostatin Human genes 0.000 claims description 3
- 108010079505 Endostatins Proteins 0.000 claims description 3
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 3
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 3
- 102100026720 Interferon beta Human genes 0.000 claims description 3
- 102000003996 Interferon-beta Human genes 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 108060008245 Thrombospondin Proteins 0.000 claims description 3
- 102000002938 Thrombospondin Human genes 0.000 claims description 3
- 208000008385 Urogenital Neoplasms Diseases 0.000 claims description 3
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 229960001388 interferon-beta Drugs 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 201000011531 vascular cancer Diseases 0.000 claims description 3
- 201000005787 hematologic cancer Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 230000002103 transcriptional effect Effects 0.000 claims description 2
- 230000001919 adrenal effect Effects 0.000 claims 4
- 210000005068 bladder tissue Anatomy 0.000 claims 4
- 210000005013 brain tissue Anatomy 0.000 claims 4
- 210000002808 connective tissue Anatomy 0.000 claims 4
- 230000000968 intestinal effect Effects 0.000 claims 4
- 210000005228 liver tissue Anatomy 0.000 claims 4
- 230000002611 ovarian Effects 0.000 claims 4
- 210000004923 pancreatic tissue Anatomy 0.000 claims 4
- 230000002792 vascular Effects 0.000 claims 4
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 1
- 238000001514 detection method Methods 0.000 abstract description 6
- 238000002619 cancer immunotherapy Methods 0.000 abstract 1
- 108020003175 receptors Proteins 0.000 description 33
- 102000005962 receptors Human genes 0.000 description 33
- 239000000427 antigen Substances 0.000 description 19
- 108091007433 antigens Proteins 0.000 description 19
- 102000036639 antigens Human genes 0.000 description 19
- 230000034994 death Effects 0.000 description 18
- 239000003814 drug Substances 0.000 description 15
- 210000001744 T-lymphocyte Anatomy 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000002163 immunogen Effects 0.000 description 12
- 230000002601 intratumoral effect Effects 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- 206010054094 Tumour necrosis Diseases 0.000 description 10
- 210000004443 dendritic cell Anatomy 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 210000001165 lymph node Anatomy 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000013059 nephrectomy Methods 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 238000009739 binding Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 5
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 5
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 210000001616 monocyte Anatomy 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 210000001672 ovary Anatomy 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 4
- 241000699694 Gerbillinae Species 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- 108010065805 Interleukin-12 Proteins 0.000 description 4
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 4
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 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 4
- 238000004220 aggregation Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 244000309464 bull Species 0.000 description 4
- 210000003679 cervix uteri Anatomy 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000003238 esophagus Anatomy 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 210000002356 skeleton Anatomy 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 230000002381 testicular Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 210000004291 uterus Anatomy 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- 241000282898 Sus scrofa Species 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000003184 complementary RNA Substances 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 230000010399 physical interaction Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 210000000512 proximal kidney tubule Anatomy 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 241000283725 Bos Species 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 102000000018 Chemokine CCL2 Human genes 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 108010008655 Epstein-Barr Virus Nuclear Antigens Proteins 0.000 description 2
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108090000176 Interleukin-13 Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 2
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 2
- 102100022430 Melanocyte protein PMEL Human genes 0.000 description 2
- 108010063954 Mucins Proteins 0.000 description 2
- 101001117316 Mus musculus Programmed cell death 1 ligand 1 Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 241001504519 Papio ursinus Species 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108020004518 RNA Probes Proteins 0.000 description 2
- 239000003391 RNA probe Substances 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 206010064390 Tumour invasion Diseases 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 210000004100 adrenal gland Anatomy 0.000 description 2
- 230000000961 alloantigen Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000009400 cancer invasion Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 230000003325 follicular Effects 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 239000012642 immune effector Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000002096 quantum dot Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 108091008023 transcriptional regulators Proteins 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BNIFSVVAHBLNTN-XKKUQSFHSA-N (2s)-4-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-4-amino-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexan Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O)CCC1 BNIFSVVAHBLNTN-XKKUQSFHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical group NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100037982 Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A Human genes 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100035526 B melanoma antigen 1 Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 101100124795 Caenorhabditis elegans hsp-110 gene Proteins 0.000 description 1
- 102100029968 Calreticulin Human genes 0.000 description 1
- 108090000549 Calreticulin Proteins 0.000 description 1
- 241000178270 Canarypox virus Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 description 1
- 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 description 1
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 description 1
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010008707 Mucin-1 Proteins 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 108010008705 Mucin-2 Proteins 0.000 description 1
- 102100034263 Mucin-2 Human genes 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 102000036673 PRAME Human genes 0.000 description 1
- 108060006580 PRAME Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 206010045240 Type I hypersensitivity Diseases 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010034034 alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase Proteins 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Chemical group C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000003443 bladder cell Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 101150052825 dnaK gene Proteins 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- -1 etc.) Proteins 0.000 description 1
- 230000004761 fibrosis Effects 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
- 238000009472 formulation Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010008714 glucose-regulated protein 170 Proteins 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 102000048776 human CD274 Human genes 0.000 description 1
- 102000049409 human MOK Human genes 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000012296 in situ hybridization assay Methods 0.000 description 1
- 231100000405 induce cancer Toxicity 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 201000010205 kidney benign neoplasm Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000000231 kidney cortex Anatomy 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000003810 lymphokine-activated killer cell Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 108700025647 major vault Proteins 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000012737 microarray-based gene expression Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 108010012038 peptide 78 Proteins 0.000 description 1
- 229940125863 peptide 78 Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- 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
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- 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
- A61K38/20—Interleukins [IL]
- A61K38/2026—IL-4
-
- 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
- A61K38/20—Interleukins [IL]
- A61K38/2066—IL-10
-
- 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
- A61K38/20—Interleukins [IL]
- A61K38/208—IL-12
-
- 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
- A61K38/20—Interleukins [IL]
- A61K38/2086—IL-13 to IL-16
-
- 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
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
- A61K38/21—Interferons [IFN]
- A61K38/215—IFN-beta
-
- 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
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
- G01N33/56972—White blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- General Engineering & Computer Science (AREA)
- Hospice & Palliative Care (AREA)
- Tropical Medicine & Parasitology (AREA)
- Plant Pathology (AREA)
- Physiology (AREA)
- Virology (AREA)
Abstract
Description
本発明は、癌組織において発現する免疫分子、および特に腫瘍細胞および腫瘍浸潤白血球における免疫分子の発現の評価に関連する。
癌の開始および進行の重要な決定要因は、癌細胞の、宿主の免疫系を回避する能力である。例えば、不適当な、不適切な、または阻害性の免疫分子が癌組織に存在することは、宿主の、癌に対する免疫反応を産生する能力を制限し得る。
本発明は、部分的には、腎細胞癌(RCC)被験体において、死亡の危険性は、同時刺激ヒト糖タンパク質B7−H1を発現する、腫瘍細胞および/または腫瘍中の白血球の数に比例するという発見に基づく。本明細書中で使用される場合、「B7−H1」という用語は、あらゆる哺乳類種由来のB7−H1を指し、そして「hB7−H1」という用語は、ヒトB7−H1を指す。B7−H1ポリペプチドおよび核酸についてのさらなる詳細は、米国特許第6,803,192号および同時係属中の米国出願連続番号第09/649,108号において提供され、その開示はその全体として本明細書中で参考文献に組み込まれる。
本発明者は、同時刺激糖タンパク質hB7−H1を発現する、増加したレベルの腫瘍細胞および/または腫瘍浸潤白血球を有する腎細胞癌(RCC)被験体は、RCCによる死亡の増加した危険性を有することを発見した。それに加えて、増加したレベルのhB7−H1発現腫瘍細胞および/または腫瘍浸潤白血球は、より高い悪性度の腫瘍と関係しており、そしてこの関連は、例えば腫瘍、リンパ節、転移(TNM)ステージ;原発性腫瘍サイズ;核グレード;および組織学的腫瘍壊死を含む、RCCの進行の伝統的な前兆に関して調整した後でも持続した。
本発明は、被験体において癌を診断する方法を提供する。その方法は、(a)組織の癌を有することが疑われる、または発症する見込みのある被験体由来の組織サンプルを提供すること、そのサンプルは試験細胞を含み、その試験細胞は組織の細胞または組織に浸潤する白血球である;および(b)その試験細胞がB7−H1を発現しているかどうかを評価することを含む。いくらかまたは全ての試験細胞による発現は、その被験体が癌を有することを示す。広く様々な癌細胞がその表面にB7−H1を発現するので、本発明の方法は、あらゆるそのような癌を診断するために特に有用である。従って試験細胞は、例えば乳房細胞、肺細胞、大腸細胞、膵臓細胞、腎細胞、胃細胞、肝細胞、骨細胞、血液細胞(例えばリンパ系細胞、顆粒球性細胞、単球またはマクロファージ)、神経組織細胞、メラニン細胞、卵巣細胞、精巣細胞、前立腺細胞、子宮頚部細胞、膣細胞、膀胱細胞、または本明細書中で列挙されたあらゆる他の細胞であり得る。さらに、試験細胞は、上記で列挙された試験細胞のいずれかを含む関連組織に存在する白血球であり得る。組織に浸潤している白血球は、T細胞(CD4+T細胞および/またはCD8+T細胞)またはBリンパ球であり得る。そのような白血球はまた、好中球、好酸球、好塩基球、単球、マクロファージ、組織球またはナチュラルキラー細胞であり得る。被験体は哺乳類であり得、そして例えばヒト、非ヒト霊長類(例えばサル、ヒヒ、またはチンパンジー)、ウマ、ウシ(または雄ウシ(oxen)または雄ウシ(bulls))、ブタ、ヒツジ、ヤギ、ネコ、ウサギ、モルモット、ハムスター、ラット、スナネズミ、またはマウスを含む。
本発明の別の局面は、免疫療法の候補を同定する方法である。この方法は、組織の癌を有する被験体から組織サンプルを提供することを含む。その組織サンプルは試験細胞を含み、その試験細胞は癌細胞または腫瘍浸潤白血球である。B7−H1を発現する、組織サンプルにおける試験細胞のレベルを評価し、もしB7−H1発現が試験細胞において検出されなければ、または免疫−阻害閾値レベルより少ない試験細胞がB7−H1を発現するなら、その被験体はより免疫療法から利益を得る見込みがある。
別の実施態様において、本発明は、癌を有する被験体の予後を決定する方法を特色とする。この方法は、(a)組織の癌を有する被験体由来の組織サンプルを提供すること、その組織サンプルは試験細胞を含み、その試験細胞は癌細胞または腫瘍浸潤白血球である;および(b)B7−H1を発現する、組織サンプルにおける試験細胞のレベルを評価することを含む。予後レベル、または予後レベルより多い試験細胞がB7−H1を発現するなら、その被験体は、予後レベルより少ない試験細胞がB7−H1を発現するよりも、より癌で死亡する可能性が高い。予後レベルは、当該分野で公知の統計学的臨床分析、例えば本明細書中で記載されるものを行うことによって得られる、前もって決定された値である。
本発明はまた、治療の方法を含む。その方法は、(a)癌を有する被験体を同定すること、いくらかまたは全ての癌細胞、またはいくらかまたは全ての癌の腫瘍浸潤白血球がB7−H1を発現している;および(b)被験体に、B7−H1およびB7−H1の受容体間の相互作用に干渉する薬剤を送達することを含み得る。これらの方法を、上記で記載した方法のいずれかの実施に続いて、またはそれ無しで行い得る。その薬剤は、抗体または例えばB7−H1に結合するFab’、F(ab’)2、またはscFv断片のような、抗体断片であり得る。その薬剤はまた、可溶性B7−H1またはB7−H1の可溶性機能的断片;B7−H1の可溶性受容体またはその可溶性機能的断片;B7−H1の受容体、例えばPD−1受容体に結合する抗体または抗体断片であり得る。PD−1受容体は、米国特許第6,808,710号においてより詳しく記載され、その開示はその全体として本明細書中で参考文献に組み込まれる。
本発明の別の局面は、腫瘍細胞または腫瘍浸潤白血球において、B7−H1の発現を阻害する方法である。その方法は:(a)癌を有する被験体を同定すること、その癌はB7−H1を発現する標的細胞を含み、その標的細胞は腫瘍細胞または腫瘍浸潤白血球である;および(b)標的細胞に:(i)B7−H1転写物にハイブリダイズするアンチセンスオリゴヌクレオチド、細胞においてB7−H1の発現を阻害するアンチセンスオリゴヌクレオチド;または(ii)B7−H1干渉RNA(RNAi)を導入することを含む。これらの方法を、上記で記載した方法のいずれかの実施に続いて、またはそれ無しに、実施し得る。
(被験体の選択)
Mayo Clinic Institutional Review Boardからの承認において、2000年から2002年の間に、一側性、弧発性明細胞RCCのために根治的腎摘出術または腎保存手術で以前に治療された、429人の被験体がMayo Clinic Nephrectomy Registryから同定された。病理的な特徴および被験体の予後はRCCのサブタイプによって異なるので、全ての分析は、最もよくあるRCCサブタイプである、明細胞RCCのみで治療した被験体に制限した[Chevilleら(2003)Am.J.Surg.Pathol.27:612−624]。hB7−H1特異的モノクローナル抗体、5H1(下記を参照のこと)は、新鮮凍結した組織を再現性良く染色し得るが、パラフィン固定した組織はしないので[Dongら(2002)Nature Med.8:793−800]、新鮮凍結組織の入手可能性に基づいて被験体を選択した。
調査した病理的特徴は、組織学的サブタイプ、腫瘍サイズ、原発性腫瘍の病期、局所リンパ節の関与、および腎摘出術(2002TNM)における遠隔転移、核グレード、および組織学的腫瘍壊死を含んでいた。全ての標本からの顕微鏡スライドを、被験体の予後の予備知識無しで、泌尿器病理学者が再調査した。組織学的サブタイプを、the Union Internationale Contre le Cancer、American Joint Committee on Cancer、およびHeidelbergガイドライン[Storkelら(1997)Cancer 80:987−989;Kovacsら(1997)J.Pathol.183:131−133]によって分類した。核グレードを、標準化された基準を用いて指定した[Lohseら(2002)Am.J.Clin.Pathol.118:877−886]。組織学的腫瘍壊死を、あらゆる顕微鏡的凝固性腫瘍壊死の存在として定義した。硝子化、出血、および線維症のような変性性の変化は、壊死とは考えなかった。
RCC腫瘍および正常腎皮質標本から作成した凍結切片(5μmの厚さ)を、Superfrost Plusスライドに載せ、空気乾燥し、そして氷冷アセトン中で固定した。Dako AutostainerおよびDako Cytomation Labeled Polymer(EnVision+)HRP検出キットTM(Dako;Carpinteria、California)を用いて染色した。スライドを、H2O2で10分間固定し、続いて1次抗B7−H1抗体と30分間室温でインキュベートした。次いで西洋ワサビペルオキシダーゼ結合2次試薬(ヤギ抗マウス免疫グロブリン)を、室温で15分間スライドに適用し、続いて発色基質と10分間インキュベートした。最後に、切片を修飾シュミットヘマトキシリンで3分間対比染色した。この研究において使用した1次抗体は5H1、マウス抗hB7−H1モノクローナル抗体であった[Dongら(2002)NatureMed.8:793−800]。良性腎腫瘍および末梢T細胞は、この研究において染色されなかった。hB7−H1染色のポジティブ組織コントロールは、ヒト扁桃腺組織であった。無関係のアイソタイプ一致抗体を、非特異的染色のコントロールのために使用した。
hB7−H1に関して陽性に染色された腫瘍細胞および白血球の割合を、被験体の予後の予備知識無しに、泌尿器病理学者が、5−10%の増加量で定量した。白血球浸潤の程度を評価し、そして無し、限局的(散乱したリンパ凝集物)、中程度、または顕著と記録した。白血球性hB7−H1発現を表す調整スコアを、白血球浸潤の程度(0=無し、1=限局的、2=中程度、3=顕著)をかけた、hB7−H1に関して陽性に染色された白血球の割合として計算した。
病理学的特徴およびhB7−H1発現間の比較を、χ二乗検定、Fisher正確確率検定、およびウィルコクソン順位和検定を用いて評価した。癌特異的な生存率を、Kaplan−Meier法を用いて推定した。フォローアップの期間を、腎摘出術の日から死亡または最後のフォローアップの日まで計算した。死因を、死亡証明書または医師の書状から決定した。hB7−H1に関して陽性に染色された細胞の割合対観察された生存率およびコックス比例ハザード回帰モデル(公式にはMartingale residualとして知られる)から予測される生存率における差異のスキャッタープロットを、hB7−H1発現に関する潜在的なカットオフポイントを同定するために使用した[Therneauら(2000)Modeling Survival Data: Extending the Cox Model、第1版(Springer−Verlag、Ann Arbor)、87−92頁]。これらのカットポイントとRCCによる死亡の関連を、コックス比例ハザード回帰モデルを用いて一変量で、そして原発性腫瘍の病期、局所リンパ節の関与、遠隔転移、腫瘍サイズ、核グレード、および組織学的腫瘍壊死に関して一度に1つの特徴を調整した後、評価する。hB7−H1発現とRCCによる死亡の関連をまた、MayoClinic SSIGN(病期、サイズ、グレード、および壊死)スコア、明細胞RCCを有する被験体のために特に開発された予後複合スコアに関して調整した[Frankら(2002)J.Urol.168:2395−2400]。SASソフトウェアパッケージ(SAS Institute、Cary、North Carolina)を用いて統計学的分析を行い、そして<0.05のp値を、統計学的に有意であると考えた。
研究に適格な429人の被験体のうち、196人(46%)が、検査調査のために利用可能な新鮮凍結組織を有していた。新鮮凍結組織を有する被験体は、有さない被験体と比較して、より大きな腫瘍を有していた(腫瘍サイズ中央値6.0cm対5.0cm;p=0.008)。しかし、研究した他の特徴は2つのグループで有意に異なっていなかった。さらに、新鮮凍結組織を有するおよび有さない被験体間で、癌特異的生存率に統計学的に有意な差異は存在しなかった(p=0.314)。
196個の明細胞RCC標本の免疫組織化学的染色は、RCC腫瘍細胞によるhB7−H1発現が無いことか、またはRCC腫瘍細胞および/またはRCC腫瘍浸潤白血球によって発現される様々な程度のhB7−H1を明らかにした(表1および2および図1)。それに加えて、RCC腫瘍が発生すると考えられる腎皮質内の近位尿細管は、研究した20個の正常腎皮質標本の中でhB7−H1発現を示さなかった(図1)。
Claims (60)
- 癌を有する被験体の予後を決定する方法であって、該方法は以下:
(a)組織の癌を有する被験体からの該組織のサンプルを提供する工程であって、ここで該組織サンプルは試験細胞を含み、該試験細胞は癌細胞または腫瘍浸潤白血球である、工程;および
(b)該組織サンプルにおける、B7−H1を発現する試験細胞のレベルを評価する工程であって、ここで予後レベルの該試験細胞、または予後レベルより多くの該試験細胞がB7−H1を発現する場合、該被験体は、予後レベルより少ない該試験細胞がB7−H1を発現する場合よりも、該癌で死亡する確率が高い、工程
を、包含する方法。 - 請求項1に記載の方法であって、前記評価する工程は、B7−H1ポリペプチドを検出することを含む、方法。
- 請求項2に記載の方法であって、前記検出する工程は、前記組織サンプルを前記B7−H1ポリペプチドに結合する抗体と接触させることを含む、方法。
- 請求項2に記載の方法であって、前記検出する工程は、蛍光フローサイトメトリー(FFC)を含む、方法。
- 請求項2に記載の方法であって、前記検出する工程は、免疫組織学を含む、方法。
- 請求項1に記載の方法であって、前記評価する工程は、B7−H1 mRNAを検出することを含む、方法。
- 請求項6に記載の方法であって、前記検出する工程は、前記サンプルを前記B7−H1 mRNAにハイブリダイズする核酸プローブと接触させることを含む、方法。
- 請求項6に記載の方法であって、前記検出する工程は、逆転写酵素−ポリメラーゼ連鎖反応を含む、方法。
- 請求項6に記載の方法であって、前記検出する工程は、インサイチューハイブリダイゼーションを含む、方法。
- 請求項1に記載の方法であって、前記組織は、肺組織、上皮組織、結合組織、血管組織、筋肉組織、神経組織、骨格組織、リンパ組織、前立腺組織、子宮頚部組織、乳房組織、脾臓組織、胃組織、腸組織、口腔組織、食道組織、皮膚組織、肝臓組織、膀胱組織、甲状腺組織、胸腺組織、副腎組織、脳組織、胆嚢組織、膵臓組織、子宮組織、卵巣組織、および精巣組織から成るグループから選択される、方法。
- 請求項1に記載の方法であって、前記組織は腎組織である、方法。
- 請求項1に記載の方法であって、前記組織の前記癌は腎細胞癌である、方法。
- 請求項1に記載の方法であって、前記被験体は哺乳類である、方法。
- 請求項13に記載の方法であって、前記哺乳類はヒトである、方法。
- 診断の方法であって、該方法は以下:
(a)組織の癌を有することが疑われる、または該組織の癌を発症する見込みのある被験体からの該組織のサンプルを提供する工程であって、ここで該サンプルは試験細胞を含み、該試験細胞は、該組織の細胞または該組織に浸潤している白血球である、工程;および
(b)該試験細胞がB7−H1を発現しているかどうかを評価する工程であって、ここでいくつかまたは全ての該試験細胞による発現は、該被験体が癌を有することを示す、工程
を、包含する方法。 - 請求項15に記載の方法であって、前記評価する工程は、B7−H1ポリペプチドを検出することを含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、前記組織サンプルを前記B7−H1ポリペプチドに結合する抗体と接触させることを含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、蛍光フローサイトメトリー(FFC)を含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、免疫組織学を含む、方法。
- 請求項15に記載の方法であって、前記評価する工程は、B7−H1 mRNAを検出することを含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、前記サンプルを前記B7−H1 mRNAにハイブリダイズする核酸プローブと接触させることを含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、逆転写酵素−ポリメラーゼ連鎖反応を含む、方法。
- 請求項16に記載の方法であって、前記検出する工程は、インサイチューハイブリダイゼーションを含む、方法。
- 請求項15に記載の方法であって、前記組織は、肺組織、上皮組織、結合組織、血管組織、筋肉組織、神経組織、骨格組織、リンパ組織、前立腺組織、子宮頚部組織、乳房組織、脾臓組織、胃組織、腸組織、口腔組織、食道組織、皮膚組織、肝臓組織、膀胱組織、甲状腺組織、胸腺組織、副腎組織、脳組織、胆嚢組織、膵臓組織、子宮組織、卵巣組織、および精巣組織から成るグループから選択される、方法。
- 請求項15に記載の方法であって、前記組織は腎組織である、方法。
- 請求項15に記載の方法であって、前記被験体は哺乳類である、方法。
- 請求項26に記載の方法であって、前記哺乳類はヒトである、方法。
- 免疫療法の候補を同定する方法であって、該方法は、以下:
(a)組織の癌を有する被験体からの組織サンプルを提供する工程であって、ここで該組織サンプルは試験細胞を含み、該試験細胞は癌細胞または腫瘍浸潤白血球である、工程;および
(b)該組織サンプルにおける、B7−H1を発現する試験細胞のレベルを評価する工程であって、ここでB7−H1発現が該試験細胞において検出されない場合、または免疫阻害閾値レベルより少ない該試験細胞がB7−H1を発現する場合、該被験体は免疫療法から利益を得る可能性がより高い、工程
を、包含する方法。 - 請求項28に記載の方法であって、前記評価する工程は、B7−H1ポリペプチドを検出することを含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、前記組織サンプルを前記B7−H1ポリペプチドに結合する抗体と接触させることを含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、蛍光フローサイトメトリー(FFC)を含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、免疫組織学を含む、方法。
- 請求項28に記載の方法であって、前記評価する工程は、B7−H1 mRNAを検出することを含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、前記サンプルを前記B7−H1 mRNAにハイブリダイズする核酸プローブと接触させることを含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、逆転写酵素−ポリメラーゼ連鎖反応を含む、方法。
- 請求項29に記載の方法であって、前記検出する工程は、インサイチューハイブリダイゼーションを含む、方法。
- 請求項28に記載の方法であって、前記組織は、肺組織、上皮組織、結合組織、血管組織、筋肉組織、神経組織、骨格組織、リンパ組織、前立腺組織、子宮頚部組織、乳房組織、脾臓組織、胃組織、腸組織、口腔組織、食道組織、皮膚組織、肝臓組織、膀胱組織、甲状腺組織、胸腺組織、副腎組織、脳組織、胆嚢組織、膵臓組織、子宮組織、卵巣組織、および精巣組織から成るグループから選択される、方法。
- 請求項28に記載の方法であって、前記組織は腎組織である、方法。
- 請求項28に記載の方法であって、前記組織の前記癌は腎細胞癌である、方法。
- 請求項28に記載の方法であって、前記被験体は哺乳類である、方法。
- 請求項40に記載の方法であって、前記哺乳類はヒトである、方法。
- 治療の方法であって、該方法は、以下:
(a)癌を有する被験体を同定する工程であって、ここでいくつかまたは全ての該癌の細胞またはいくつかまたは全ての該癌の腫瘍浸潤白血球はB7−H1を発現する、工程;および
(b)該被験体にB7−H1とB7−H1の受容体との間の相互作用に干渉する薬剤を送達する工程、
を、包含する方法。 - 請求項42に記載の方法であって、前記薬剤は抗体またはその断片を含む、方法。
- 請求項42に記載の方法であって、前記薬剤はB7−H1に結合する、方法。
- 請求項42に記載の方法であって、前記薬剤はB7−H1の受容体に結合する、方法。
- 請求項45に記載の方法であって、前記受容体はPD−1である、方法。
- 請求項44に記載の方法であって、前記薬剤はB7−H1の組み換え可溶性受容体である、方法。
- 請求項43に記載の方法であって、前記抗体断片は、Fab’断片、F(ab’)2断片、または1本鎖Fv(sFv)断片からなるグループから選択される、方法。
- 請求項42に記載の方法であって、前記被験体に1種またはそれ以上の免疫調節性サイトカイン、成長因子、または血管新生抑制因子を送達することをさらに含む、方法。
- 請求項49に記載の方法であって、前記1種またはそれ以上の免疫調節性サイトカイン、成長因子、または血管新生抑制因子は、インターロイキン(IL)−1〜25、インターフェロン−γ(IFN−γ)、インターフェロン−α(IFN−α)、インターフェロン−β(IFN−β)、インターフェロン−γ(IFN−γ)、腫瘍壊死因子−α(TNF−α)、顆粒球マクロファージコロニー刺激因子(GM−CSF)、顆粒球コロニー刺激因子(G−CSF)、エンドスタチン、アンジオスタチン、およびトロンボスポンジンからなるグループから選択される、方法。
- 請求項42に記載の方法であって、前記癌は、血液癌、神経癌、黒色腫、乳癌、肺癌、頭頚部癌、胃腸癌、肝臓癌、膵臓癌、腎臓癌、尿生殖器癌、骨癌、または血管癌からなるグループから選択される、方法。
- 請求項42に記載の方法であって、前記癌は腎細胞癌である、方法。
- 腫瘍細胞または腫瘍浸潤白血球においてB7−H1の発現を阻害する方法であって、該方法は以下:(a)癌を有する被験体を同定する工程であって、該癌はB7−H1を発現する標的細胞を含み、該標的細胞は腫瘍細胞または腫瘍浸潤白血球である、工程;および(b)該標的細胞に:(i)B7−H1転写物にハイブリダイズするアンチセンスオリゴヌクレオチドであって、ここで該アンチセンスオリゴヌクレオチドは該細胞においてB7−H1の発現を阻害する、アンチセンスオリゴヌクレオチド;または(ii)B7−H1干渉RNA(RNAi)を導入する工程、を包含する方法。
- 請求項53に記載の方法であって、前記導入工程は、前記アンチセンスオリゴヌクレオチドまたは前記RNAiの前記被験体への投与、および該アンチセンスオリゴヌクレオチドまたは該RNAiの前記標的細胞による取り込みを包含する、方法。
- 請求項53に記載の方法であって、前記導入工程は、前記アンチセンスオリゴヌクレオチドに相補的なヌクレオチド配列に作動可能に連結した転写調節因子(TRE)を含む核酸の前記被験体への投与、および前記細胞による取り込みを包含し、ここで該細胞内での該ヌクレオチド配列の転写は、該アンチセンスオリゴヌクレオチドを産生する、方法。
- 請求項53に記載の方法であって、前記導入工程は、(a)前記RNAiのセンス鎖およびアンチセンス鎖が、別のTREの指示下で転写され得る核酸;または(b)該RNAiのセンス鎖およびアンチセンス鎖の両方が、単一のTREの指示下で転写され得る核酸の、前記被験体への投与、および前記細胞による取り込みを包含する、方法。
- 請求項53に記載の方法であって、前記被験体は哺乳類である、方法。
- 請求項57に記載の方法であって、前記哺乳類はヒトである、方法。
- 請求項53に記載の方法であって、前記癌は腎細胞癌である、方法。
- 請求項53に記載の方法であって、前記癌は、肺組織、上皮組織、結合組織、血管組織、神経組織、骨格組織、リンパ組織、前立腺組織、子宮頚部組織、乳房組織、脾臓組織、胃組織、腸組織、口腔組織、食道組織、皮膚組織、肝臓組織、膀胱組織、甲状腺組織、胸腺組織、副腎組織、脳組織、胆嚢組織、膵臓組織、子宮組織、卵巣組織、および精巣組織から成るグループから選択される組織の癌である、方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61659004P | 2004-10-06 | 2004-10-06 | |
US60/616,590 | 2004-10-06 | ||
US64279405P | 2005-01-11 | 2005-01-11 | |
US60/642,794 | 2005-01-11 | ||
PCT/US2005/036431 WO2006042237A2 (en) | 2004-10-06 | 2005-10-06 | B7-h1 and methods of diagnosis, prognosis, and treatment of cancer |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013059449A Division JP2013128495A (ja) | 2004-10-06 | 2013-03-22 | B7−h1ならびに癌の診断、予後診断および処置の方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2008515442A true JP2008515442A (ja) | 2008-05-15 |
JP2008515442A5 JP2008515442A5 (ja) | 2008-11-20 |
JP5303146B2 JP5303146B2 (ja) | 2013-10-02 |
Family
ID=36148995
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007535894A Active JP5303146B2 (ja) | 2004-10-06 | 2005-10-06 | B7−h1ならびに癌の診断、予後診断および処置の方法 |
JP2013059449A Withdrawn JP2013128495A (ja) | 2004-10-06 | 2013-03-22 | B7−h1ならびに癌の診断、予後診断および処置の方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013059449A Withdrawn JP2013128495A (ja) | 2004-10-06 | 2013-03-22 | B7−h1ならびに癌の診断、予後診断および処置の方法 |
Country Status (15)
Country | Link |
---|---|
US (10) | US7892540B2 (ja) |
EP (2) | EP1810026B1 (ja) |
JP (2) | JP5303146B2 (ja) |
AU (1) | AU2005295038B2 (ja) |
CA (2) | CA2583257C (ja) |
CY (1) | CY1120423T1 (ja) |
DK (1) | DK1810026T3 (ja) |
ES (1) | ES2671893T3 (ja) |
HK (1) | HK1116249A1 (ja) |
HU (1) | HUE039237T2 (ja) |
MX (1) | MX2007004176A (ja) |
PL (1) | PL1810026T3 (ja) |
PT (1) | PT1810026T (ja) |
SI (1) | SI1810026T1 (ja) |
WO (1) | WO2006042237A2 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013523162A (ja) * | 2010-04-06 | 2013-06-17 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Cd274/pd−l1遺伝子の発現を阻害するための組成物および方法 |
US10889813B2 (en) | 2015-09-02 | 2021-01-12 | Alnylam Pharmaceuticals, Inc. | Programmed cell death 1 ligand 1 (PD-L1) iRNA compositions and methods of use thereof |
JP2022034059A (ja) * | 2016-03-14 | 2022-03-02 | エフ.ホフマン-ラ ロシュ アーゲー | Pd-l1発現低減用のオリゴヌクレオチド |
Families Citing this family (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3016482A1 (en) * | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
AU2005295038B2 (en) | 2004-10-06 | 2012-05-17 | Mayo Foundation For Medical Education And Research | B7-H1 and methods of diagnosis, prognosis, and treatment of cancer |
CN101213297B (zh) | 2005-05-09 | 2013-02-13 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及单独使用或与其它免疫治疗剂联合使用抗pd-1抗体来治疗癌症的方法 |
CA2981431C (en) | 2005-06-08 | 2021-04-13 | Dana-Farber Cancer Institute Inc. | Use of compounds that reduce activity or expression of programmed cell death-1 to treat lymphoma |
KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
EP1777523A1 (en) * | 2005-10-19 | 2007-04-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | An in vitro method for the prognosis of progression of a cancer and of the outcome in a patient and means for performing said method |
WO2007082144A2 (en) * | 2006-01-05 | 2007-07-19 | Mayo Foundation For Medical Education And Research | B7-h1 and survivin in cancer |
US20090215084A1 (en) * | 2006-01-05 | 2009-08-27 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
WO2007124361A2 (en) * | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
US20090304711A1 (en) * | 2006-09-20 | 2009-12-10 | Drew Pardoll | Combinatorial Therapy of Cancer and Infectious Diseases with Anti-B7-H1 Antibodies |
WO2008058018A2 (en) | 2006-11-02 | 2008-05-15 | Mayo Foundation For Medical Education And Research | Predicting cancer outcome |
EP2133365B1 (en) * | 2006-12-27 | 2017-05-17 | Emory University | Compositions and methods for the treatment of infections and tumors |
JP5265140B2 (ja) * | 2007-06-14 | 2013-08-14 | 学校法人日本医科大学 | 卵巣癌の検出方法及び検出用キット |
KR101586617B1 (ko) | 2007-06-18 | 2016-01-20 | 머크 샤프 앤 도메 비.브이. | 사람 프로그램된 사멸 수용체 pd-1에 대한 항체 |
US20100285039A1 (en) * | 2008-01-03 | 2010-11-11 | The Johns Hopkins University | B7-H1 (CD274) Antagonists Induce Apoptosis of Tumor Cells |
US20110020325A1 (en) * | 2008-02-29 | 2011-01-27 | Kwon Eugene D | Methods for reducing granulomatous inflammation |
CN102014937A (zh) | 2008-03-03 | 2011-04-13 | 迈阿密大学 | 基于异基因癌细胞的免疫治疗 |
CA2725978A1 (en) | 2008-05-28 | 2009-12-03 | Genomedx Biosciences, Inc. | Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer |
US10407731B2 (en) | 2008-05-30 | 2019-09-10 | Mayo Foundation For Medical Education And Research | Biomarker panels for predicting prostate cancer outcomes |
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 |
WO2010027802A2 (en) * | 2008-08-25 | 2010-03-11 | New York University | Methods for treating diabetic wounds |
CN102203125A (zh) * | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
NZ591130A (en) * | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
US8541170B2 (en) | 2008-11-17 | 2013-09-24 | Veracyte, Inc. | Methods and compositions of molecular profiling for disease diagnostics |
US9495515B1 (en) | 2009-12-09 | 2016-11-15 | Veracyte, Inc. | Algorithms for disease diagnostics |
US10236078B2 (en) | 2008-11-17 | 2019-03-19 | Veracyte, Inc. | Methods for processing or analyzing a sample of thyroid tissue |
HUE028582T2 (en) * | 2008-11-28 | 2016-12-28 | Univ Emory | Method for determining the efficacy of PD-1 antagonists |
PE20120341A1 (es) * | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
US9074258B2 (en) | 2009-03-04 | 2015-07-07 | Genomedx Biosciences Inc. | Compositions and methods for classifying thyroid nodule disease |
WO2010129934A2 (en) | 2009-05-07 | 2010-11-11 | Veracyte, Inc. | Methods and compositions for diagnosis of thyroid conditions |
US10446272B2 (en) | 2009-12-09 | 2019-10-15 | Veracyte, Inc. | Methods and compositions for classification of samples |
US20110312520A1 (en) | 2010-05-11 | 2011-12-22 | Veracyte, Inc. | Methods and compositions for diagnosing conditions |
US9254310B2 (en) | 2010-06-17 | 2016-02-09 | New York University | Therapeutic and cosmetic uses and applications of calreticulin |
US20140315973A1 (en) * | 2010-10-07 | 2014-10-23 | Agency For Science, Technology And Research | Parp-1 inhibitors |
EP2791359B1 (en) | 2011-12-13 | 2020-01-15 | Decipher Biosciences, Inc. | Cancer diagnostics using non-coding transcripts |
BR122022015975B1 (pt) * | 2012-05-15 | 2024-01-02 | Bristol-Myers Squibb Company | Anticorpos monoclonais, kit para o tratamento de um indivíduo afligido com um câncer, processo para medir pd-l1 membranoso em células tumorais isoladas e uso do anticorpo ou uma porção que se liga ao antígeno do mesmo |
AR091649A1 (es) | 2012-07-02 | 2015-02-18 | Bristol Myers Squibb Co | Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos |
US11035005B2 (en) | 2012-08-16 | 2021-06-15 | Decipher Biosciences, Inc. | Cancer diagnostics using biomarkers |
US9302005B2 (en) | 2013-03-14 | 2016-04-05 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
KR20230070054A (ko) * | 2013-03-15 | 2023-05-19 | 제넨테크, 인크. | Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법 |
US11976329B2 (en) | 2013-03-15 | 2024-05-07 | Veracyte, Inc. | Methods and systems for detecting usual interstitial pneumonia |
CN105378104A (zh) | 2013-03-15 | 2016-03-02 | 威拉赛特公司 | 用于样品分类的方法和组合物 |
BR122023024195A2 (pt) | 2013-09-20 | 2023-12-26 | Bristol-Myers Squibb Company | Usos de anticorpos anti-lag-3 e anticorpos anti-pd-1 |
EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
ES2714708T3 (es) | 2013-10-01 | 2019-05-29 | Mayo Found Medical Education & Res | Procedimientos para el tratamiento de cáncer en pacientes con niveles elevados de Bim |
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 |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
WO2015179654A1 (en) | 2014-05-22 | 2015-11-26 | Mayo Foundation For Medical Education And Research | Distinguishing antagonistic and agonistic anti b7-h1 antibodies |
JP6666905B2 (ja) | 2014-05-29 | 2020-03-18 | スプリング バイオサイエンス コーポレーション | Pd−l1抗体及びその使用 |
EP3149481B1 (en) | 2014-05-30 | 2019-01-09 | Ventana Medical Systems, Inc. | Multiplex assay for improved scoring of tumor tissues stained for pd-l1 |
US20160009805A1 (en) | 2014-07-11 | 2016-01-14 | Genentech, Inc. | Anti-pd-l1 antibodies and diagnostic uses thereof |
EP3171896A4 (en) | 2014-07-23 | 2018-03-21 | Mayo Foundation for Medical Education and Research | Targeting dna-pkcs and b7-h1 to treat cancer |
WO2016040882A1 (en) | 2014-09-13 | 2016-03-17 | Novartis Ag | Combination therapies of egfr inhibitors |
BR112017007379A2 (pt) | 2014-10-14 | 2017-12-19 | Dana Farber Cancer Inst Inc | moléculas de anticorpo para pd-l1 e usos das mesmas |
EP3770274A1 (en) | 2014-11-05 | 2021-01-27 | Veracyte, Inc. | Systems and methods of diagnosing idiopathic pulmonary fibrosis on transbronchial biopsies using machine learning and high dimensional transcriptional data |
AU2015360667B2 (en) | 2014-12-09 | 2021-09-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized cluster of differentiation 274 gene |
GB201500319D0 (en) * | 2015-01-09 | 2015-02-25 | Agency Science Tech & Res | Anti-PD-L1 antibodies |
EP3254110B1 (en) | 2015-02-03 | 2020-03-18 | Ventana Medical Systems, Inc. | Histochemical assay for evaluating expression of programmed death ligand 1 (pd-l1) |
MA41460A (fr) | 2015-02-03 | 2017-12-12 | Oncomed Pharm Inc | Agents de liaison à la tnfrsf et leurs utilisations |
US10336824B2 (en) | 2015-03-13 | 2019-07-02 | Cytomx Therapeutics, Inc. | Anti-PDL1 antibodies, activatable anti-PDL1 antibodies, and methods of thereof |
WO2016149350A1 (en) | 2015-03-17 | 2016-09-22 | Mayo Foundation For Medical Education And Research | Methods and materials for assessing and treating cancer |
KR20180040138A (ko) | 2015-07-13 | 2018-04-19 | 싸이톰스 테라퓨틱스, 인크. | 항pd-1 항체, 활성화 가능한 항pd-1 항체, 및 이들의 사용 방법 |
WO2017024465A1 (en) | 2015-08-10 | 2017-02-16 | Innovent Biologics (Suzhou) Co., Ltd. | Pd-1 antibodies |
IL293385A (en) | 2015-08-11 | 2022-07-01 | Omniab Inc | New anti–pd–1 antibodies |
AR105654A1 (es) | 2015-08-24 | 2017-10-25 | Lilly Co Eli | Anticuerpos pd-l1 (ligando 1 de muerte celular programada) |
MX2018002315A (es) | 2015-09-01 | 2018-04-11 | Agenus Inc | Anticuerpos anti muerte programada 1 (pd 1) y metodos de uso de los mismos. |
AR106184A1 (es) | 2015-09-29 | 2017-12-20 | Celgene Corp | Proteínas de unión a pd-1 y sus métodos de uso |
US20180318365A1 (en) | 2015-10-19 | 2018-11-08 | Cold Genesys, Inc. | Methods of treating solid or lymphatic tumors by combination therapy |
WO2017075045A2 (en) | 2015-10-30 | 2017-05-04 | Mayo Foundation For Medical Education And Research | Antibodies to b7-h1 |
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 |
US9567399B1 (en) * | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
AU2017281497B2 (en) | 2016-06-22 | 2023-04-06 | Proqr Therapeutics Ii B.V. | Single-stranded RNA-editing oligonucleotides |
TWI760352B (zh) | 2016-08-09 | 2022-04-11 | 英商克馬伯有限公司 | 抗icos抗體 |
EP3504348B1 (en) | 2016-08-24 | 2022-12-14 | Decipher Biosciences, Inc. | Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy |
WO2018048936A1 (en) | 2016-09-06 | 2018-03-15 | Incelldx, Inc. | Methods of detecting per cell pd-l1 expression and uses thereof |
US11726089B2 (en) | 2016-09-06 | 2023-08-15 | Incelldx, Inc. | Methods of assaying neoplastic and neoplasia-related cells and uses thereof |
KR102257154B1 (ko) | 2016-09-19 | 2021-05-28 | 셀진 코포레이션 | Pd-1 결합 단백질을 사용하는 면역 질환의 치료 방법 |
WO2018053401A1 (en) | 2016-09-19 | 2018-03-22 | Celgene Corporation | Methods of treating vitiligo using pd-1 binding proteins |
EP3523434A1 (en) | 2016-10-07 | 2019-08-14 | Secarna Pharmaceuticals GmbH & Co. KG | Novel approach for treating cancer |
EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
JP7106538B2 (ja) | 2016-12-07 | 2022-07-26 | アジェナス インコーポレイテッド | 抗体およびその使用方法 |
WO2018132916A1 (en) | 2017-01-20 | 2018-07-26 | Genomedx Biosciences, Inc. | Molecular subtyping, prognosis, and treatment of bladder cancer |
US11873532B2 (en) | 2017-03-09 | 2024-01-16 | Decipher Biosciences, Inc. | Subtyping prostate cancer to predict response to hormone therapy |
WO2018205035A1 (en) | 2017-05-12 | 2018-11-15 | Genomedx Biosciences, Inc | Genetic signatures to predict prostate cancer metastasis and identify tumor agressiveness |
EP3630813A1 (en) | 2017-05-24 | 2020-04-08 | Novartis AG | Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer |
HUE065242T2 (hu) | 2017-05-30 | 2024-05-28 | Bristol Myers Squibb Co | LAG-3-pozitív tumorok kezelése |
CA3065304A1 (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 |
CN110914302A (zh) | 2017-06-01 | 2020-03-24 | 赛托姆克斯治疗学股份有限公司 | 可活化抗pdl1抗体及其使用方法 |
GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
US11217329B1 (en) | 2017-06-23 | 2022-01-04 | Veracyte, Inc. | Methods and systems for determining biological sample integrity |
US11629189B2 (en) | 2017-12-19 | 2023-04-18 | Kymab Limited | Bispecific antibody for ICOS and PD-L1 |
US20210198374A1 (en) | 2018-04-17 | 2021-07-01 | Celldex Therapeutics, Inc. | Anti-cd27 and anti-pd-l1 antibodies and bispecific constructs |
US11142524B2 (en) | 2018-08-01 | 2021-10-12 | Stingray Therapeutics, Inc. | Substituted-3H-imidazo[4,5-c]pyridine and 1H-pyrrolo[2,3-c]pyridine series of novel Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1) and stimulator for interferon genes (STING) modulators as cancer immunotherapeutics |
WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
US20220107320A1 (en) | 2019-02-15 | 2022-04-07 | Incelldx, Inc. | Assaying Bladder-Associated Samples, Identifying and Treating Bladder-Associated Neoplasia, and Kits for Use Therein |
WO2020201144A1 (en) | 2019-04-02 | 2020-10-08 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for immunotherapy |
EP3963074A1 (en) | 2019-05-03 | 2022-03-09 | Secarna Pharmaceuticals GmbH & Co. KG | Pd-l1 antisense oligonucleotides for use in tumor treatment |
CN114423793A (zh) | 2019-09-18 | 2022-04-29 | 分子模板公司 | 包含志贺菌毒素a亚基支架的pd-l1结合分子 |
US11918649B2 (en) | 2019-09-18 | 2024-03-05 | Molecular Templates, Inc. | PD-L1-binding molecules comprising Shiga toxin a subunit scaffolds |
Family Cites Families (166)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3687808A (en) * | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US4034074A (en) * | 1974-09-19 | 1977-07-05 | The Board Of Trustees Of Leland Stanford Junior University | Universal reagent 2-site immunoradiometric assay using labelled anti (IgG) |
US4036945A (en) * | 1976-05-03 | 1977-07-19 | The Massachusetts General Hospital | Composition and method for determining the size and location of myocardial infarcts |
US4098876A (en) * | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
US4233402A (en) | 1978-04-05 | 1980-11-11 | Syva Company | Reagents and method employing channeling |
US4272398A (en) * | 1978-08-17 | 1981-06-09 | The United States Of America As Represented By The Secretary Of Agriculture | Microencapsulation process |
US4257774A (en) * | 1979-07-16 | 1981-03-24 | Meloy Laboratories, Inc. | Intercalation inhibition assay for compounds that interact with DNA or RNA |
US4331647A (en) * | 1980-03-03 | 1982-05-25 | Goldenberg Milton David | Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers |
US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US5155020A (en) | 1989-03-08 | 1992-10-13 | Health Research Inc. | Recombinant poxvirus host range selection system |
US4769330A (en) | 1981-12-24 | 1988-09-06 | Health Research, Incorporated | Modified vaccinia virus and methods for making and using the same |
ATE64618T1 (de) | 1982-03-15 | 1991-07-15 | Schering Corp | Hybride dns, damit hergestellte bindungszusammensetzung und verfahren dafuer. |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4650764A (en) * | 1983-04-12 | 1987-03-17 | Wisconsin Alumni Research Foundation | Helper cell |
JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
US5235033A (en) * | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US4861719A (en) * | 1986-04-25 | 1989-08-29 | Fred Hutchinson Cancer Research Center | DNA constructs for retrovirus packaging cell lines |
AU610083B2 (en) * | 1986-08-18 | 1991-05-16 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents |
US4946778A (en) * | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US4987071A (en) * | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
US4980289A (en) | 1987-04-27 | 1990-12-25 | Wisconsin Alumni Research Foundation | Promoter deficient retroviral vector |
US4861627A (en) * | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
US5254678A (en) | 1987-12-15 | 1993-10-19 | Gene Shears Pty. Limited | Ribozymes |
US6018026A (en) | 1988-01-22 | 2000-01-25 | Zymogenetics, Inc. | Biologically active dimerized and multimerized polypeptide fusions |
US5567584A (en) | 1988-01-22 | 1996-10-22 | Zymogenetics, Inc. | Methods of using biologically active dimerized polypeptide fusions to detect PDGF |
US5750375A (en) * | 1988-01-22 | 1998-05-12 | Zymogenetics, Inc. | Methods of producing secreted receptor analogs and biologically active dimerized polypeptide fusions |
EP1762623A1 (en) | 1988-01-22 | 2007-03-14 | ZymoGenetics, Inc. | Methods for producing biologically active peptide dimers |
US5278056A (en) * | 1988-02-05 | 1994-01-11 | The Trustees Of Columbia University In The City Of New York | Retroviral packaging cell lines and process of using same |
US5750666A (en) * | 1988-05-26 | 1998-05-12 | Competitve Technologies, Inc. | Polynucleotide phosphorodithioate compounds |
US6303121B1 (en) | 1992-07-30 | 2001-10-16 | Advanced Research And Technology | Method of using human receptor protein 4-1BB |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
US5124263A (en) * | 1989-01-12 | 1992-06-23 | Wisconsin Alumni Research Foundation | Recombination resistant retroviral helper cell and products produced thereby |
US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5225336A (en) * | 1989-03-08 | 1993-07-06 | Health Research Incorporated | Recombinant poxvirus host range selection system |
US5175099A (en) | 1989-05-17 | 1992-12-29 | Research Corporation Technologies, Inc. | Retrovirus-mediated secretion of recombinant products |
US5240846A (en) * | 1989-08-22 | 1993-08-31 | The Regents Of The University Of Michigan | Gene therapy vector for cystic fibrosis |
US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
ATE149841T1 (de) | 1990-01-26 | 1997-03-15 | Immunomedics Inc | Impfstoffe gegen krebs und infektionskrankheiten |
US5204243A (en) * | 1990-02-14 | 1993-04-20 | Health Research Incorporated | Recombinant poxvirus internal cores |
US5214136A (en) * | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
US5580756A (en) | 1990-03-26 | 1996-12-03 | Bristol-Myers Squibb Co. | B7Ig fusion protein |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
EP0537293A4 (en) | 1990-07-02 | 1993-09-08 | Bristol-Myers Company | Ligand for cd28 receptor on b cells and methods |
DK0585287T3 (da) | 1990-07-10 | 2000-04-17 | Cambridge Antibody Tech | Fremgangsmåde til fremstilling af specifikke bindingsparelementer |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
US5218105A (en) * | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
JPH06505704A (ja) * | 1990-09-20 | 1994-06-30 | ギリアド サイエンシズ,インコーポレイテッド | 改変ヌクレオシド間結合 |
US5296347A (en) * | 1991-02-08 | 1994-03-22 | Ciba Corning Diagnostics Corp. | Bridge immunoassay |
CA2082951C (en) * | 1991-03-15 | 1999-12-21 | Robert M. Platz | Pulmonary administration of granulocyte colony stimulating factor |
CA2112578C (en) | 1991-07-03 | 2000-10-10 | Yasuhiro Ogawa | Thermoplastic polyurethane elastomer, process for producing same, apparatus for producing same and elastomer fibers made from same |
CA2067868A1 (en) * | 1991-10-24 | 1993-04-25 | Delbert D. Randolph | Hydrometer for determining coolant fluid antifreeze concentration |
EP0671926B1 (en) | 1992-08-11 | 2002-11-13 | President And Fellows Of Harvard College | Immunomodulatory peptides |
US7211259B1 (en) * | 1993-05-07 | 2007-05-01 | Immunex Corporation | 4-1BB polypeptides and DNA encoding 4-1BB polypeptides |
US5674704A (en) | 1993-05-07 | 1997-10-07 | Immunex Corporation | Cytokine designated 4-IBB ligand |
US5942607A (en) * | 1993-07-26 | 1999-08-24 | Dana-Farber Cancer Institute | B7-2: a CTLA4/CD28 ligand |
US5861310A (en) * | 1993-11-03 | 1999-01-19 | Dana-Farber Cancer Institute | Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor |
US5858776A (en) * | 1993-11-03 | 1999-01-12 | Repligen Corporation | Tumor cells with increased immunogenicity and uses therefor |
AU7526894A (en) | 1993-08-16 | 1995-03-14 | Arch Development Corporation | B7-2: ctla4/cd28 counter receptor |
JP3926839B2 (ja) | 1993-09-14 | 2007-06-06 | エピミューン,インコーポレイティド | 万能dr−結合性ペプチドを用いる免疫応答の改変 |
AU697482B2 (en) | 1993-09-16 | 1998-10-08 | Indiana University Research And Technology Corporation | Human receptor H4-1BB |
CA2143491C (en) | 1994-03-01 | 2011-02-22 | Yasumasa Ishida | A novel peptide related to human programmed cell death and dna encoding it |
US5451569A (en) | 1994-04-19 | 1995-09-19 | Hong Kong University Of Science And Technology R & D Corporation Limited | Pulmonary drug delivery system |
US5972703A (en) * | 1994-08-12 | 1999-10-26 | The Regents Of The University Of Michigan | Bone precursor cells: compositions and methods |
WO1996029348A1 (en) | 1995-03-23 | 1996-09-26 | Indiana University Foundation | Monoclonal antibody against human receptor protein 4-1bb and methods of its use for treatment of diseases |
JP2911056B2 (ja) * | 1995-04-08 | 1999-06-23 | 株式会社エルジ化学 | ヒト4−1bbに特異的なモノクローナル抗体およびこれを産生する細胞株 |
US5675848A (en) | 1995-10-18 | 1997-10-14 | Mallinckrodt Medical, Inc. | Inflatable blanket having perforations of different sizes |
CA2235226A1 (en) | 1995-11-10 | 1997-05-15 | Elan Corporation, Plc | Peptides which enhance transport across tissues and methods of identifying and using the same |
WO1997024447A1 (en) | 1996-01-02 | 1997-07-10 | Chiron Corporation | Immunostimulation mediated by gene-modified dendritic cells |
US5874240A (en) * | 1996-03-15 | 1999-02-23 | Human Genome Sciences, Inc. | Human 4-1BB receptor splicing variant |
DE69718268D1 (de) | 1996-10-03 | 2003-02-13 | Canon Kk | Verfahren zur Detektion von Zielnukleinsäure, Verfahren zu ihrer Quantifizierung und Pyrylium-Verbindungen zur Chemilumineszenz-Analyse |
NZ334691A (en) | 1996-10-11 | 2000-12-22 | Bristol Myers Squibb Co | Compositions of anti-4-1BB antibody effective for immunomodulation and treatment of T-cell autoimmune disease |
AU736587B2 (en) | 1996-11-20 | 2001-08-02 | Yale University | Survivin, a protein that inhibits cellular apoptosis, and its modulation |
AUPO390396A0 (en) | 1996-11-29 | 1996-12-19 | Csl Limited | Novel promiscuous T helper cell epitopes |
EP1012275A1 (en) | 1997-01-31 | 2000-06-28 | University Of Rochester | Chimeric antibody fusion proteins for the recruitment and stimulation of an antitumor immune response |
WO1998036096A1 (en) | 1997-02-14 | 1998-08-20 | E.I. Du Pont De Nemours And Company | Detection of double-stranded dna in a homogeneous solution |
US20070224663A1 (en) | 1997-03-07 | 2007-09-27 | Human Genome Sciences, Inc. | Human Secreted Proteins |
US20060223088A1 (en) | 1997-03-07 | 2006-10-05 | Rosen Craig A | Human secreted proteins |
US7368531B2 (en) * | 1997-03-07 | 2008-05-06 | Human Genome Sciences, Inc. | Human secreted proteins |
US7411051B2 (en) * | 1997-03-07 | 2008-08-12 | Human Genome Sciences, Inc. | Antibodies to HDPPA04 polypeptide |
WO2001034768A2 (en) | 1999-11-09 | 2001-05-17 | Human Genome Sciences, Inc. | 15 human secreted proteins |
WO1999064597A1 (en) | 1998-06-10 | 1999-12-16 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | β2 MICROGLOBULIN FUSION PROTEINS AND HIGH AFFINITY VARIANTS |
US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
KR20000034847A (ko) | 1998-11-17 | 2000-06-26 | 성재갑 | 인간 4-1비비 분자에 대한 인간화 항체 및 이를 포함하는 약학조성물 |
US6734172B2 (en) | 1998-11-18 | 2004-05-11 | Pacific Northwest Research Institute | Surface receptor antigen vaccines |
US7041474B2 (en) * | 1998-12-30 | 2006-05-09 | Millennium Pharmaceuticals, Inc. | Nucleic acid encoding human tango 509 |
US20080213778A1 (en) | 1998-12-30 | 2008-09-04 | Millennium Pharmaceuticals, Inc. | Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses |
AU3209300A (en) | 1999-01-15 | 2000-08-01 | Mount Sinai School Of Medicine Of The City University Of New York, The | Combination therapy of cancer by the activation of co-stimulatory molecules expressed by immune cells and cytokines |
WO2000055375A1 (en) | 1999-03-17 | 2000-09-21 | Alphagene, Inc. | Secreted proteins and polynucleotides encoding them |
CZ20013527A3 (cs) | 1999-04-02 | 2002-10-16 | Corixa Corporation | Sloučeniny a způsoby pro terapii a diagnostiku karcinomu plic |
AU6117000A (en) | 1999-07-26 | 2001-02-13 | Genentech Inc. | Novel polynucleotides and method of use thereof |
EP1074617A3 (en) | 1999-07-29 | 2004-04-21 | Research Association for Biotechnology | Primers for synthesising full-length cDNA and their use |
US6423885B1 (en) * | 1999-08-13 | 2002-07-23 | Commonwealth Scientific And Industrial Research Organization (Csiro) | Methods for obtaining modified phenotypes in plant cells |
BR0013542A (pt) * | 1999-08-23 | 2002-05-14 | Dana Farber Cancer Inst Inc | Moléculas b7-4 e usos para as mesmas |
JP4896327B2 (ja) * | 1999-08-23 | 2012-03-14 | ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド | Pd−1、b7−4の受容体、およびその使用 |
CA2387959A1 (en) | 1999-11-12 | 2001-05-17 | Human Genome Sciences, Inc. | 21 human secreted proteins |
US6210289B1 (en) | 1999-11-12 | 2001-04-03 | Labrake James | Golf grip hand alignment device in combination with a golf club grip |
CA3016482A1 (en) | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
US6803192B1 (en) | 1999-11-30 | 2004-10-12 | Mayo Foundation For Medical Education And Research | B7-H1, a novel immunoregulatory molecule |
US7029365B2 (en) | 2000-02-17 | 2006-04-18 | Applied Materials Inc. | Pad assembly for electrochemical mechanical processing |
AU4721901A (en) | 2000-02-25 | 2001-09-03 | Immunex Corp | Integrin antagonists |
US20030165831A1 (en) | 2000-03-21 | 2003-09-04 | John Lee | Novel genes, compositions, kits, and methods for identification, assessment, prevention, and therapy of ovarian cancer |
AU2001259063A1 (en) * | 2000-04-12 | 2001-10-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US7030219B2 (en) * | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
US6965018B2 (en) | 2000-06-06 | 2005-11-15 | Bristol-Myers Squibb Company | Antibodies directed to B7-related polypeptide, BSL-2 |
US20030031675A1 (en) * | 2000-06-06 | 2003-02-13 | Mikesell Glen E. | B7-related nucleic acids and polypeptides useful for immunomodulation |
JP2004501624A (ja) | 2000-06-28 | 2004-01-22 | ジェネティックス・インスチチュート・リミテッド・ライアビリティ・カンパニー | Pd−l2分子:新規pd−1リガンドおよびその使用 |
EP1301524A1 (en) | 2000-06-30 | 2003-04-16 | Human Genome Sciences, Inc. | B7-like polynucleotides, polypeptides, and antibodies |
DE60123617T2 (de) | 2000-07-05 | 2007-08-16 | Vogue Pool Products, La Salle | Übergrundschwimmbeckentragestruktur |
US6635750B1 (en) | 2000-07-20 | 2003-10-21 | Millennium Pharmaceuticals, Inc. | B7-H2 nucleic acids, members of the B7 family |
WO2002010187A1 (en) * | 2000-07-27 | 2002-02-07 | Mayo Foundation For Medical Education And Research | B7-h3 and b7-h4, novel immunoregulatory molecules |
ATE532860T1 (de) | 2000-09-20 | 2011-11-15 | Amgen Inc | B7-ähnliche moleküle und deren anwendungen |
US20040247563A1 (en) | 2000-11-02 | 2004-12-09 | Lynch David H. | Method of enhancing lymphocyte-mediated immune responses |
US20040209263A1 (en) | 2000-12-07 | 2004-10-21 | Clawson Gary A. | Selection of catalytic nucleic acids targeted to infectious agents |
CA2433313A1 (en) | 2000-12-19 | 2002-07-25 | Curagen Corporation | Polypetides and nucleic acids encoding same |
US20030180309A1 (en) | 2001-01-08 | 2003-09-25 | Baum Peter R. | Human B7 polypeptides |
US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
US6743619B1 (en) * | 2001-01-30 | 2004-06-01 | Nuvelo | Nucleic acids and polypeptides |
WO2003008583A2 (en) | 2001-03-02 | 2003-01-30 | Sagres Discovery | Novel compositions and methods for cancer |
US20030109434A1 (en) * | 2001-03-19 | 2003-06-12 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of kidney cancer |
EP2388590A1 (en) * | 2001-04-02 | 2011-11-23 | Dana Farber Cancer Institute | PD-1, a receptor for B7-4, and uses thereof |
AR036993A1 (es) * | 2001-04-02 | 2004-10-20 | Wyeth Corp | Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas |
US20060084794A1 (en) * | 2001-04-12 | 2006-04-20 | Human Genome Sciences, Inc. | Albumin fusion proteins |
AU2002258941A1 (en) * | 2001-04-20 | 2002-11-05 | Mayo Foundation For Medical Education And Research | Methods of enhancing cell responsiveness |
WO2005007855A2 (en) | 2003-07-14 | 2005-01-27 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF B7-H1 GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US20060276422A1 (en) * | 2001-05-18 | 2006-12-07 | Nassim Usman | RNA interference mediated inhibition of B7-H1 gene expression using short interfering nucleic acid (siNA) |
AU2002322211A1 (en) | 2001-07-12 | 2003-01-29 | Canvac | Methods and compisitions for activation human t cells in vitro |
US7651686B2 (en) * | 2001-10-09 | 2010-01-26 | Mayo Foundation For Medical Education And Research | Enhancement of immune responses by 4-1bb-binding agents |
ATE384783T1 (de) | 2001-10-19 | 2008-02-15 | Zymogenetics Inc | Dimerisierter wachstumsfaktor sowie materialien und verfahren zu seiner herstellung |
CA2466279A1 (en) * | 2001-11-13 | 2003-05-22 | Dana-Farber Cancer Institute, Inc. | Agents that modulate immune cell activation and methods of use thereof |
US7164500B2 (en) * | 2002-01-29 | 2007-01-16 | Hewlett-Packard Development Company, L.P. | Method and apparatus for the automatic generation of image capture device control marks |
ES2654064T3 (es) | 2002-07-03 | 2024-03-13 | Ono Pharmaceutical Co | Composiciones inmunopotenciadoras que comprenden anticuerpos anti-PD-L1 |
JP2005536511A (ja) * | 2002-07-15 | 2005-12-02 | マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ | 4−1bb結合物質を用いる治療及び予防 |
US7769423B2 (en) * | 2002-09-11 | 2010-08-03 | Duke University | MRI imageable liposomes for the evaluation of treatment efficacy, thermal distribution, and demonstration of dose painting |
US7432351B1 (en) | 2002-10-04 | 2008-10-07 | Mayo Foundation For Medical Education And Research | B7-H1 variants |
US7449300B2 (en) | 2002-11-21 | 2008-11-11 | Mayo Foundation For Medical Education And Research | Detection of antibodies specific for B7-H1 in subjects with diseases or pathological conditions mediated by activated T cells |
ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
US7563869B2 (en) * | 2003-01-23 | 2009-07-21 | Ono Pharmaceutical Co., Ltd. | Substance specific to human PD-1 |
GB0303663D0 (en) | 2003-02-18 | 2003-03-19 | Lorantis Ltd | Assays and medical treatments |
CA2516588A1 (en) | 2003-02-27 | 2004-09-10 | Mount Sinai Hospital | Assay for detection of renal cell carcinoma |
TWM248611U (en) | 2003-11-28 | 2004-11-01 | Lite On Technology Corp | Paper-feeding tray structure |
KR100518346B1 (ko) * | 2003-12-01 | 2005-09-29 | 현대모비스 주식회사 | 스티어링 기어 일체형 프레임 구조 |
ATE517914T1 (de) * | 2004-03-08 | 2011-08-15 | Zymogenetics Inc | Dimere fusionsproteine und materialien und verfahren zu deren herstellung |
AU2005295038B2 (en) | 2004-10-06 | 2012-05-17 | Mayo Foundation For Medical Education And Research | B7-H1 and methods of diagnosis, prognosis, and treatment of cancer |
EP1814568A4 (en) | 2004-10-29 | 2009-08-12 | Univ Southern California | ANTI-CANCER POLYIMMUNOTHERAPY IN WHICH CO-STIMULATING MOLECULES ARE USED |
CA2981431C (en) * | 2005-06-08 | 2021-04-13 | Dana-Farber Cancer Institute Inc. | Use of compounds that reduce activity or expression of programmed cell death-1 to treat lymphoma |
US20070231344A1 (en) | 2005-10-28 | 2007-10-04 | The Brigham And Women's Hospital, Inc. | Conjugate vaccines for non-proteinaceous antigens |
US20090215084A1 (en) | 2006-01-05 | 2009-08-27 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
WO2007082144A2 (en) * | 2006-01-05 | 2007-07-19 | Mayo Foundation For Medical Education And Research | B7-h1 and survivin in cancer |
JP5093097B2 (ja) | 2006-03-03 | 2012-12-05 | 小野薬品工業株式会社 | 細胞表面機能分子の細胞外領域多量体 |
WO2007124361A2 (en) * | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
WO2008037080A1 (en) | 2006-09-29 | 2008-04-03 | Universite De Montreal | Methods and compositions for immune response modulation and uses thereof |
EP2133365B1 (en) | 2006-12-27 | 2017-05-17 | Emory University | Compositions and methods for the treatment of infections and tumors |
WO2009029342A2 (en) | 2007-07-13 | 2009-03-05 | The Johns Hopkins University | B7-dc variants |
EP2185689A2 (en) | 2007-08-09 | 2010-05-19 | Genzyme Corporation | Method of treating autoimmune disease with mesenchymal stem cells |
US20110020325A1 (en) * | 2008-02-29 | 2011-01-27 | Kwon Eugene D | Methods for reducing granulomatous inflammation |
WO2009114110A1 (en) | 2008-03-08 | 2009-09-17 | Immungene, Inc. | Engineered fusion molecules immunotherapy in cancer and inflammatory diseases |
CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
NZ591130A (en) * | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
IT1395574B1 (it) | 2009-09-14 | 2012-10-16 | Guala Dispensing Spa | Dispositivo di erogazione |
WO2011066342A2 (en) | 2009-11-24 | 2011-06-03 | Amplimmune, Inc. | Simultaneous inhibition of pd-l1/pd-l2 |
-
2005
- 2005-10-06 AU AU2005295038A patent/AU2005295038B2/en active Active
- 2005-10-06 US US11/245,713 patent/US7892540B2/en active Active
- 2005-10-06 PT PT5808659T patent/PT1810026T/pt unknown
- 2005-10-06 CA CA2583257A patent/CA2583257C/en active Active
- 2005-10-06 HU HUE05808659A patent/HUE039237T2/hu unknown
- 2005-10-06 PL PL05808659T patent/PL1810026T3/pl unknown
- 2005-10-06 EP EP05808659.6A patent/EP1810026B1/en not_active Revoked
- 2005-10-06 WO PCT/US2005/036431 patent/WO2006042237A2/en active Application Filing
- 2005-10-06 DK DK05808659.6T patent/DK1810026T3/en active
- 2005-10-06 JP JP2007535894A patent/JP5303146B2/ja active Active
- 2005-10-06 SI SI200532213T patent/SI1810026T1/en unknown
- 2005-10-06 MX MX2007004176A patent/MX2007004176A/es active IP Right Grant
- 2005-10-06 EP EP18167823.6A patent/EP3428191A1/en active Pending
- 2005-10-06 CA CA2943949A patent/CA2943949C/en active Active
- 2005-10-06 ES ES05808659.6T patent/ES2671893T3/es active Active
-
2008
- 2008-05-19 HK HK08105496.0A patent/HK1116249A1/xx unknown
-
2011
- 2011-01-24 US US13/012,063 patent/US8747833B2/en active Active
-
2013
- 2013-03-22 JP JP2013059449A patent/JP2013128495A/ja not_active Withdrawn
-
2014
- 2014-04-29 US US14/264,568 patent/US20150044165A1/en not_active Abandoned
-
2015
- 2015-09-01 US US14/842,572 patent/US20160264667A1/en not_active Abandoned
-
2016
- 2016-02-18 US US15/047,445 patent/US9803015B2/en active Active
- 2016-03-14 US US15/069,258 patent/US20160257953A1/en not_active Abandoned
-
2017
- 2017-09-29 US US15/719,750 patent/US20180100015A1/en not_active Abandoned
-
2018
- 2018-02-06 US US15/890,048 patent/US20180179281A1/en not_active Abandoned
- 2018-06-14 CY CY20181100624T patent/CY1120423T1/el unknown
-
2019
- 2019-08-19 US US16/544,357 patent/US11242387B2/en active Active
-
2021
- 2021-08-13 US US17/402,262 patent/US11939378B2/en active Active
Non-Patent Citations (4)
Title |
---|
JPN6011024340; 日本外科学会雑誌,第105巻,臨時増刊号,第258頁,SF-060-3(2004年3月) * |
JPN6011024341; 日本泌尿器科学会雑誌,第95巻,第369頁,OP2-076(2004年3月) * |
JPN6011024345; Proc. Natl. Acad. Sci. USA, vol. 101, pages 17174-17179 (Dec. 2004) * |
JPN6011024347; J. Mol. Med., vol. 81, pages 281-287 (2003) * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013523162A (ja) * | 2010-04-06 | 2013-06-17 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Cd274/pd−l1遺伝子の発現を阻害するための組成物および方法 |
JP2017038600A (ja) * | 2010-04-06 | 2017-02-23 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | Cd274/pd−l1遺伝子の発現を阻害するための組成物および方法 |
JP2019047826A (ja) * | 2010-04-06 | 2019-03-28 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | Cd274/pd−l1遺伝子の発現を阻害するための組成物および方法 |
US10745704B2 (en) | 2010-04-06 | 2020-08-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of CD274/PD-L1 gene |
US10889813B2 (en) | 2015-09-02 | 2021-01-12 | Alnylam Pharmaceuticals, Inc. | Programmed cell death 1 ligand 1 (PD-L1) iRNA compositions and methods of use thereof |
JP2022034059A (ja) * | 2016-03-14 | 2022-03-02 | エフ.ホフマン-ラ ロシュ アーゲー | Pd-l1発現低減用のオリゴヌクレオチド |
JP7447073B2 (ja) | 2016-03-14 | 2024-03-11 | エフ. ホフマン-ラ ロシュ アーゲー | Pd-l1発現低減用のオリゴヌクレオチド |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5303146B2 (ja) | B7−h1ならびに癌の診断、予後診断および処置の方法 | |
Pereira et al. | Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition | |
Gómez-Aleza et al. | Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells | |
Komohara et al. | The coordinated actions of TIM-3 on cancer and myeloid cells in the regulation of tumorigenicity and clinical prognosis in clear cell renal cell carcinomas | |
Massara et al. | ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity | |
Reinart et al. | Delayed development of chronic lymphocytic leukemia in the absence of macrophage migration inhibitory factor | |
Zhang et al. | Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma | |
Yu et al. | The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation | |
Giannou et al. | NRAS destines tumor cells to the lungs | |
US20230295736A1 (en) | Compositions and methods comprising digital signatures to predict response and resistance to targeted therapy and immunotherapy | |
Kumar et al. | CXCL14 promotes a robust brain tumor-associated immune response in glioma | |
US20070253954A1 (en) | Epha4 As Therapeutic Target Of Prc And Pdaca | |
Silva et al. | Dual role of CCL3/CCR1 in oral squamous cell carcinoma: implications in tumor metastasis and local host defense | |
Theivanthiran et al. | Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti–PD-1 immunotherapy | |
CN101084438B (zh) | B7-h1和癌症的诊断、预后和治疗方法 | |
Takekoshi et al. | CCR7-expressing B16 melanoma cells downregulate interferon-γ-mediated inflammation and increase lymphangiogenesis in the tumor microenvironment | |
Rust et al. | Gene expression analysis of dendritic/Langerhans cells and Langerhans cell histiocytosis | |
Walsh et al. | Adipose contributes to CXCL5 regulated immune evasion in pancreatic cancer | |
US20150218242A1 (en) | TIF1-Gamma for Treating and Diagnosing Inflammatory Diseases |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081003 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081003 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110516 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110804 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110811 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110914 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110922 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111014 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20111014 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111128 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120227 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120305 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120316 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120810 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121101 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20121122 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130322 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130422 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130516 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130603 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130624 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5303146 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |