JP2024511029A - TGF-β阻害剤及びその使用 - Google Patents
TGF-β阻害剤及びその使用 Download PDFInfo
- Publication number
- JP2024511029A JP2024511029A JP2023557047A JP2023557047A JP2024511029A JP 2024511029 A JP2024511029 A JP 2024511029A JP 2023557047 A JP2023557047 A JP 2023557047A JP 2023557047 A JP2023557047 A JP 2023557047A JP 2024511029 A JP2024511029 A JP 2024511029A
- Authority
- JP
- Japan
- Prior art keywords
- tgfβ
- tumor
- circulating
- level
- cancer
- 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.)
- Pending
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 362
- 102000004887 Transforming Growth Factor beta Human genes 0.000 title claims description 479
- 108090001012 Transforming Growth Factor beta Proteins 0.000 title claims description 479
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 title description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 794
- 201000011510 cancer Diseases 0.000 claims abstract description 190
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 113
- 238000000034 method Methods 0.000 claims abstract description 105
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 50
- 238000011282 treatment Methods 0.000 claims description 205
- 239000000523 sample Substances 0.000 claims description 182
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 claims description 181
- 210000004027 cell Anatomy 0.000 claims description 130
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 claims description 126
- 239000000427 antigen Substances 0.000 claims description 102
- 108091007433 antigens Proteins 0.000 claims description 102
- 102000036639 antigens Human genes 0.000 claims description 102
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 97
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 97
- 230000027455 binding Effects 0.000 claims description 93
- 210000004369 blood Anatomy 0.000 claims description 92
- 239000008280 blood Substances 0.000 claims description 92
- 238000005119 centrifugation Methods 0.000 claims description 53
- 239000003814 drug Substances 0.000 claims description 50
- 238000001565 modulated differential scanning calorimetry Methods 0.000 claims description 49
- 230000009467 reduction Effects 0.000 claims description 49
- 239000012634 fragment Substances 0.000 claims description 45
- 101001004913 Homo sapiens Transforming growth factor beta activator LRRC33 Proteins 0.000 claims description 37
- 102100025954 Transforming growth factor beta activator LRRC33 Human genes 0.000 claims description 37
- 239000003446 ligand Substances 0.000 claims description 37
- 230000014509 gene expression Effects 0.000 claims description 29
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 26
- 230000007423 decrease Effects 0.000 claims description 26
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 24
- 238000003556 assay Methods 0.000 claims description 22
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 claims description 19
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 19
- 102100022338 Integrin alpha-M Human genes 0.000 claims description 19
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 19
- 230000002829 reductive effect Effects 0.000 claims description 18
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 claims description 16
- 206010005003 Bladder cancer Diseases 0.000 claims description 16
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 claims description 16
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 claims description 16
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 claims description 16
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 16
- 238000002512 chemotherapy Methods 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 16
- 230000001965 increasing effect Effects 0.000 claims description 16
- 201000001441 melanoma Diseases 0.000 claims description 16
- 230000005937 nuclear translocation Effects 0.000 claims description 16
- 238000001959 radiotherapy Methods 0.000 claims description 16
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 16
- 231100000024 genotoxic Toxicity 0.000 claims description 15
- 230000001738 genotoxic effect Effects 0.000 claims description 15
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 12
- 230000002601 intratumoral effect Effects 0.000 claims description 12
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 12
- 102100025470 Carcinoembryonic antigen-related cell adhesion molecule 8 Human genes 0.000 claims description 11
- 101000914320 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 8 Proteins 0.000 claims description 11
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 9
- 239000003146 anticoagulant agent Substances 0.000 claims description 9
- 229940127219 anticoagulant drug Drugs 0.000 claims description 9
- 229960002768 dipyridamole Drugs 0.000 claims description 9
- 208000007990 Giant Cell Tumor of Tendon Sheath Diseases 0.000 claims description 8
- 201000008754 Tenosynovial giant cell tumor Diseases 0.000 claims description 8
- 239000001509 sodium citrate Substances 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
- 206010017758 gastric cancer Diseases 0.000 claims description 7
- 201000011549 stomach cancer Diseases 0.000 claims description 7
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 108091005735 TGF-beta receptors Proteins 0.000 claims description 6
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 claims description 6
- 229960005305 adenosine Drugs 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 229960000278 theophylline Drugs 0.000 claims description 6
- 206010044412 transitional cell carcinoma Diseases 0.000 claims description 6
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 6
- 229940038773 trisodium citrate Drugs 0.000 claims description 6
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 5
- 238000002965 ELISA Methods 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 5
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 claims description 5
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 claims description 5
- 102000004211 Platelet factor 4 Human genes 0.000 claims description 5
- 108090000778 Platelet factor 4 Proteins 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 206010038389 Renal cancer Diseases 0.000 claims description 5
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims description 5
- 201000010536 head and neck cancer Diseases 0.000 claims description 5
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 5
- 201000010982 kidney cancer Diseases 0.000 claims description 5
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 4
- 108091092878 Microsatellite Proteins 0.000 claims description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 4
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 4
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 4
- 208000037844 advanced solid tumor Diseases 0.000 claims description 4
- 201000010897 colon adenocarcinoma Diseases 0.000 claims description 4
- 238000002991 immunohistochemical analysis Methods 0.000 claims description 4
- 230000001394 metastastic effect Effects 0.000 claims description 4
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 4
- 206010046766 uterine cancer Diseases 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 206010027480 Metastatic malignant melanoma Diseases 0.000 claims description 3
- 239000012661 PARP inhibitor Substances 0.000 claims description 3
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 3
- 201000000062 kidney sarcoma Diseases 0.000 claims description 3
- 208000021039 metastatic melanoma Diseases 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 208000023747 urothelial carcinoma Diseases 0.000 claims description 3
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 claims description 2
- 239000012472 biological sample Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 108020001756 ligand binding domains Proteins 0.000 claims description 2
- 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 claims 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 56
- 239000000203 mixture Substances 0.000 abstract description 29
- 230000004797 therapeutic response Effects 0.000 abstract description 27
- 238000012544 monitoring process Methods 0.000 abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 75
- 108010029485 Protein Isoforms Proteins 0.000 description 73
- 102000001708 Protein Isoforms Human genes 0.000 description 73
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 70
- 230000004044 response Effects 0.000 description 69
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 68
- 238000001994 activation Methods 0.000 description 63
- 230000004913 activation Effects 0.000 description 63
- 201000010099 disease Diseases 0.000 description 60
- 238000012545 processing Methods 0.000 description 50
- 230000005764 inhibitory process Effects 0.000 description 49
- 238000011275 oncology therapy Methods 0.000 description 42
- 238000001574 biopsy Methods 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 40
- 102000006495 integrins Human genes 0.000 description 35
- 108010044426 integrins Proteins 0.000 description 35
- 206010062016 Immunosuppression Diseases 0.000 description 33
- 102000004169 proteins and genes Human genes 0.000 description 32
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 31
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 31
- 210000002744 extracellular matrix Anatomy 0.000 description 31
- 235000018102 proteins Nutrition 0.000 description 31
- 230000011664 signaling Effects 0.000 description 31
- 229940124639 Selective inhibitor Drugs 0.000 description 30
- 210000002865 immune cell Anatomy 0.000 description 30
- 229940124597 therapeutic agent Drugs 0.000 description 30
- 210000001744 T-lymphocyte Anatomy 0.000 description 29
- 206010061598 Immunodeficiency Diseases 0.000 description 28
- 239000003102 growth factor Substances 0.000 description 28
- 230000003472 neutralizing effect Effects 0.000 description 26
- 210000001519 tissue Anatomy 0.000 description 26
- 102000008121 Latent TGF-beta Binding Proteins Human genes 0.000 description 25
- 108010049807 Latent TGF-beta Binding Proteins Proteins 0.000 description 25
- 239000005557 antagonist Substances 0.000 description 25
- 230000000694 effects Effects 0.000 description 25
- 238000002648 combination therapy Methods 0.000 description 24
- 230000007717 exclusion Effects 0.000 description 24
- 210000002540 macrophage Anatomy 0.000 description 24
- 239000000306 component Substances 0.000 description 23
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 22
- 230000008901 benefit Effects 0.000 description 22
- 239000000090 biomarker Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 230000008859 change Effects 0.000 description 19
- 239000012740 non-selective inhibitor Substances 0.000 description 19
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 19
- 108010005323 integrin alpha8beta1 Proteins 0.000 description 18
- 230000001988 toxicity Effects 0.000 description 18
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 17
- 210000001616 monocyte Anatomy 0.000 description 17
- 206010028537 myelofibrosis Diseases 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- 230000037361 pathway Effects 0.000 description 16
- 238000002203 pretreatment Methods 0.000 description 16
- 231100000419 toxicity Toxicity 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 15
- 238000011269 treatment regimen Methods 0.000 description 15
- 108060003951 Immunoglobulin Proteins 0.000 description 14
- 238000012575 bio-layer interferometry Methods 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 102000018358 immunoglobulin Human genes 0.000 description 14
- 230000000495 immunoinflammatory effect Effects 0.000 description 14
- 238000009169 immunotherapy Methods 0.000 description 14
- 102000006354 HLA-DR Antigens Human genes 0.000 description 13
- 108010058597 HLA-DR Antigens Proteins 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 239000011159 matrix material Substances 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 102000004127 Cytokines Human genes 0.000 description 12
- 108090000695 Cytokines Proteins 0.000 description 12
- 206010016654 Fibrosis Diseases 0.000 description 12
- 210000004322 M2 macrophage Anatomy 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 12
- 230000004761 fibrosis Effects 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 210000004698 lymphocyte Anatomy 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 230000008482 dysregulation Effects 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 231100000682 maximum tolerated dose Toxicity 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 238000013188 needle biopsy Methods 0.000 description 11
- 229960002621 pembrolizumab Drugs 0.000 description 11
- 239000000092 prognostic biomarker Substances 0.000 description 11
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 11
- 230000035772 mutation Effects 0.000 description 10
- 229960003301 nivolumab Drugs 0.000 description 10
- 210000002381 plasma Anatomy 0.000 description 10
- 231100000041 toxicology testing Toxicity 0.000 description 10
- 241000282412 Homo Species 0.000 description 9
- 238000011374 additional therapy Methods 0.000 description 9
- 102000025171 antigen binding proteins Human genes 0.000 description 9
- 108091000831 antigen binding proteins Proteins 0.000 description 9
- 238000013459 approach Methods 0.000 description 9
- 229950002916 avelumab Drugs 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 210000000987 immune system Anatomy 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 210000000651 myofibroblast Anatomy 0.000 description 9
- 230000036961 partial effect Effects 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 8
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 230000002411 adverse Effects 0.000 description 8
- 239000012503 blood component Substances 0.000 description 8
- 238000004590 computer program Methods 0.000 description 8
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 8
- 229950009791 durvalumab Drugs 0.000 description 8
- 210000002950 fibroblast Anatomy 0.000 description 8
- 230000028993 immune response Effects 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 208000003476 primary myelofibrosis Diseases 0.000 description 8
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 8
- 210000005166 vasculature Anatomy 0.000 description 8
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 7
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 7
- 102000009618 Transforming Growth Factors Human genes 0.000 description 7
- 108010009583 Transforming Growth Factors Proteins 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 210000001772 blood platelet Anatomy 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 230000001747 exhibiting effect Effects 0.000 description 7
- 230000005746 immune checkpoint blockade Effects 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000010534 mechanism of action Effects 0.000 description 7
- 231100000062 no-observed-adverse-effect level Toxicity 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 210000003289 regulatory T cell Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 108010009992 CD163 antigen Proteins 0.000 description 6
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 6
- 101000576894 Homo sapiens Macrophage mannose receptor 1 Proteins 0.000 description 6
- 102100025354 Macrophage mannose receptor 1 Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102100025831 Scavenger receptor cysteine-rich type 1 protein M130 Human genes 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 210000000612 antigen-presenting cell Anatomy 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 229960003852 atezolizumab Drugs 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 239000002458 cell surface marker Substances 0.000 description 6
- 231100000433 cytotoxic Toxicity 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- 210000003162 effector t lymphocyte Anatomy 0.000 description 6
- 230000003176 fibrotic effect Effects 0.000 description 6
- 230000009545 invasion Effects 0.000 description 6
- 230000036210 malignancy Effects 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 210000000066 myeloid cell Anatomy 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 102000001398 Granzyme Human genes 0.000 description 5
- 108060005986 Granzyme Proteins 0.000 description 5
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 5
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 5
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 5
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 5
- 208000014767 Myeloproliferative disease Diseases 0.000 description 5
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 5
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 5
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 5
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 230000006023 anti-tumor response Effects 0.000 description 5
- 229940121418 budigalimab Drugs 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 229940121420 cemiplimab Drugs 0.000 description 5
- 210000003690 classically activated macrophage Anatomy 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000000539 dimer Substances 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 206010020718 hyperplasia Diseases 0.000 description 5
- 210000005008 immunosuppressive cell Anatomy 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 229960005386 ipilimumab Drugs 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 238000010801 machine learning Methods 0.000 description 5
- 230000003211 malignant effect Effects 0.000 description 5
- 208000037819 metastatic cancer Diseases 0.000 description 5
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 5
- 230000008520 organization Effects 0.000 description 5
- 229930192851 perforin Natural products 0.000 description 5
- 239000003642 reactive oxygen metabolite Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000011285 therapeutic regimen Methods 0.000 description 5
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 4
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 4
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 4
- 102100025136 Macrosialin Human genes 0.000 description 4
- 108010085220 Multiprotein Complexes Proteins 0.000 description 4
- 102000007474 Multiprotein Complexes Human genes 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- 206010033128 Ovarian cancer Diseases 0.000 description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- 230000001594 aberrant effect Effects 0.000 description 4
- 238000004422 calculation algorithm Methods 0.000 description 4
- 238000002619 cancer immunotherapy Methods 0.000 description 4
- 229940022399 cancer vaccine Drugs 0.000 description 4
- 238000009566 cancer vaccine Methods 0.000 description 4
- 230000004087 circulation Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 230000006054 immunological memory Effects 0.000 description 4
- 238000012744 immunostaining Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 210000003071 memory t lymphocyte Anatomy 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 230000003439 radiotherapeutic effect Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000004043 responsiveness Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229940066453 tecentriq Drugs 0.000 description 4
- 238000011287 therapeutic dose Methods 0.000 description 4
- 229940055760 yervoy Drugs 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 3
- -1 Itga11 Proteins 0.000 description 3
- IVRXNBXKWIJUQB-UHFFFAOYSA-N LY-2157299 Chemical compound CC1=CC=CC(C=2C(=C3CCCN3N=2)C=2C3=CC(=CC=C3N=CC=2)C(N)=O)=N1 IVRXNBXKWIJUQB-UHFFFAOYSA-N 0.000 description 3
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 3
- 230000009830 antibody antigen interaction Effects 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011220 combination immunotherapy Methods 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 229950000456 galunisertib Drugs 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 238000000099 in vitro assay Methods 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 238000010827 pathological analysis Methods 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 230000004983 pleiotropic effect Effects 0.000 description 3
- 208000037821 progressive disease Diseases 0.000 description 3
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000002123 temporal effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000009827 uniform distribution Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- UZOSBNQFZUJWFP-UHFFFAOYSA-N 4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide;hydrate Chemical compound O.CC1=CC=CC(C=2C(=C3CCCN3N=2)C=2C3=CC(=CC=C3N=CC=2)C(N)=O)=N1 UZOSBNQFZUJWFP-UHFFFAOYSA-N 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 101150008656 COL1A1 gene Proteins 0.000 description 2
- 208000030808 Clear cell renal carcinoma Diseases 0.000 description 2
- 101150008975 Col3a1 gene Proteins 0.000 description 2
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 2
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102100029995 DNA ligase 1 Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102100035233 Furin Human genes 0.000 description 2
- 108090001126 Furin Proteins 0.000 description 2
- 102000014015 Growth Differentiation Factors Human genes 0.000 description 2
- 108010050777 Growth Differentiation Factors Proteins 0.000 description 2
- 101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 2
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 2
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 2
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 2
- 101000662009 Homo sapiens UDP-N-acetylglucosamine pyrophosphorylase Proteins 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 102000002698 KIR Receptors Human genes 0.000 description 2
- 108010043610 KIR Receptors Proteins 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028561 Myeloid metaplasia Diseases 0.000 description 2
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 102100025386 Oxidized low-density lipoprotein receptor 1 Human genes 0.000 description 2
- 101710199789 Oxidized low-density lipoprotein receptor 1 Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108091005682 Receptor kinases Proteins 0.000 description 2
- 108010011702 Transforming Growth Factor-beta Type I Receptor Proteins 0.000 description 2
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 2
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 2
- 206010064390 Tumour invasion Diseases 0.000 description 2
- 102100037921 UDP-N-acetylglucosamine pyrophosphorylase Human genes 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 208000017733 acquired polycythemia vera Diseases 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000009400 cancer invasion Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 208000030381 cutaneous melanoma Diseases 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000011496 digital image analysis Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
- 229940056913 eftilagimod alfa Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 102000054751 human RUNX1T1 Human genes 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000005934 immune activation Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 2
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940125798 integrin inhibitor Drugs 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 2
- 230000015654 memory Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical group C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000004802 monitoring treatment efficacy Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 230000006780 non-homologous end joining Effects 0.000 description 2
- 244000309459 oncolytic virus Species 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000009038 pharmacological inhibition Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 238000000678 plasma activation Methods 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 208000037244 polycythemia vera Diseases 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 108091011138 protein binding proteins Proteins 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000004447 silicone coating Substances 0.000 description 2
- 201000003708 skin melanoma Diseases 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000012085 transcriptional profiling Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- CWOFQJBATWQSHL-DEOSSOPVSA-N (2S)-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(quinazolin-4-ylamino)butanoic acid Chemical compound COCCN(CCCCc1ccc2CCCNc2n1)CC[C@H](Nc1ncnc2ccccc12)C(O)=O CWOFQJBATWQSHL-DEOSSOPVSA-N 0.000 description 1
- ONKCBKDTKZIWHZ-MRWFHJSOSA-N (4r)-4-[[(2r)-6-amino-2-[[(2r)-2-[[4-(aminocarbamothioylamino)benzoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[(2r)-1-amino-6-[bis[2-[[4-[2-(1h-imidazol-5-yl)ethylamino]-4-oxobutanoyl]amino]acetyl]amino]-1-oxohexan-2-yl]amino]-5-oxope Chemical compound C([C@H](C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN(C(=O)CNC(=O)CCC(=O)NCCC=1NC=NC=1)C(=O)CNC(=O)CCC(=O)NCCC=1NC=NC=1)C(N)=O)NC(=O)C=1C=CC(NC(=S)NN)=CC=1)C1=CC=C(O)C=C1 ONKCBKDTKZIWHZ-MRWFHJSOSA-N 0.000 description 1
- 101150072006 33 gene Proteins 0.000 description 1
- 101150020966 Acta2 gene Proteins 0.000 description 1
- 102100036732 Actin, aortic smooth muscle Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 229940125565 BMS-986016 Drugs 0.000 description 1
- 208000027188 Bifid uvula Diseases 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 208000013627 Camurati-Engelmann disease Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 208000004652 Cardiovascular Abnormalities Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010264 Condition aggravated Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 101710148291 DNA ligase 1 Proteins 0.000 description 1
- 102100035474 DNA polymerase kappa Human genes 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 208000013558 Developmental Bone disease Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101710088235 Envelope glycoprotein C homolog Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102100027281 Fanconi anemia group F protein Human genes 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 101150099704 Fn1 gene Proteins 0.000 description 1
- 206010018276 Gingival bleeding Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000771075 Homo sapiens Cyclic nucleotide-gated cation channel beta-1 Proteins 0.000 description 1
- 101000863770 Homo sapiens DNA ligase 1 Proteins 0.000 description 1
- 101001094659 Homo sapiens DNA polymerase kappa Proteins 0.000 description 1
- 101000865085 Homo sapiens DNA polymerase theta Proteins 0.000 description 1
- 101001054659 Homo sapiens Latent-transforming growth factor beta-binding protein 1 Proteins 0.000 description 1
- 101001054646 Homo sapiens Latent-transforming growth factor beta-binding protein 3 Proteins 0.000 description 1
- 101000619640 Homo sapiens Leucine-rich repeats and immunoglobulin-like domains protein 1 Proteins 0.000 description 1
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101001004924 Homo sapiens Transforming growth factor beta activator LRRC32 Proteins 0.000 description 1
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 108091082332 JAK family Proteins 0.000 description 1
- 101150043981 LOXL2 gene Proteins 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 208000001826 Marfan syndrome Diseases 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 208000032818 Microsatellite Instability Diseases 0.000 description 1
- 101150106019 Mmp2 gene Proteins 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 229940126021 PLN-74809 Drugs 0.000 description 1
- 102100035031 Palladin Human genes 0.000 description 1
- 101710128215 Palladin Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 102100038603 Probable ubiquitin carboxyl-terminal hydrolase FAF-X Human genes 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 108091007744 Programmed cell death receptors Proteins 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000003837 Second Primary Neoplasms Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 206010072610 Skeletal dysplasia Diseases 0.000 description 1
- 230000006044 T cell activation 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
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 102000043168 TGF-beta family Human genes 0.000 description 1
- 108091085018 TGF-beta family Proteins 0.000 description 1
- 102100033456 TGF-beta receptor type-1 Human genes 0.000 description 1
- 101150000629 TGFB1 gene Proteins 0.000 description 1
- 238000012338 Therapeutic targeting Methods 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000014172 Transforming Growth Factor-beta Type I Receptor Human genes 0.000 description 1
- 101710169743 Transforming growth factor beta activator LRRC33 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 102100035071 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 231100000230 acceptable toxicity Toxicity 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 108091022873 acetoacetate decarboxylase Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 229940062810 apitegromab Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000117 blood based biomarker Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000037966 cold tumor Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010252 digital analysis Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 108060002895 fibrillin Proteins 0.000 description 1
- 102000013370 fibrillin Human genes 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229950004003 fresolimumab Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000004545 gene duplication Effects 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 238000013427 histology analysis Methods 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 102000052917 human LRRC32 Human genes 0.000 description 1
- 102000053077 human LTBP1 Human genes 0.000 description 1
- 102000053454 human LTBP3 Human genes 0.000 description 1
- 102000048304 human NRROS Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 108010042442 integrin alphaEbeta7 Proteins 0.000 description 1
- 108010021315 integrin beta7 Proteins 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000012923 label-free technique Methods 0.000 description 1
- 210000004901 leucine-rich repeat Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004460 liquid liquid chromatography Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 210000001806 memory b lymphocyte Anatomy 0.000 description 1
- 208000037843 metastatic solid tumor Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000001167 myeloblast Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 201000002740 oral squamous cell carcinoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007331 pathological accumulation Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 230000036279 refractory period Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000008093 supporting effect Effects 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
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 230000002100 tumorsuppressive effect Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00113—Growth factors
- A61K39/001134—Transforming growth factor [TGF]
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- 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
-
- 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
- G01N33/5011—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 for testing antineoplastic activity
-
- 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
-
- 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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/495—Transforming growth factor [TGF]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Mycology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163166824P | 2021-03-26 | 2021-03-26 | |
US63/166,824 | 2021-03-26 | ||
US202163202260P | 2021-06-03 | 2021-06-03 | |
US63/202,260 | 2021-06-03 | ||
US202263302999P | 2022-01-25 | 2022-01-25 | |
US63/302,999 | 2022-01-25 | ||
US202263313386P | 2022-02-24 | 2022-02-24 | |
US63/313,386 | 2022-02-24 | ||
PCT/US2022/022063 WO2022204581A2 (fr) | 2021-03-26 | 2022-03-25 | Inhibiteurs de tgf-bêta et leur utilisation |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2024511029A true JP2024511029A (ja) | 2024-03-12 |
Family
ID=88149091
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023557047A Pending JP2024511029A (ja) | 2021-03-26 | 2022-03-25 | TGF-β阻害剤及びその使用 |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP4314831A2 (fr) |
JP (1) | JP2024511029A (fr) |
AU (1) | AU2022243575A1 (fr) |
CA (1) | CA3213216A1 (fr) |
IL (1) | IL306049A (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024187051A1 (fr) * | 2023-03-07 | 2024-09-12 | Scholar Rock, Inc. | Inhibiteurs de tgf-bêta destinés à être utilisés pour traiter un cancer résistant ou réfractaire chez des patients |
-
2022
- 2022-03-25 CA CA3213216A patent/CA3213216A1/fr active Pending
- 2022-03-25 IL IL306049A patent/IL306049A/en unknown
- 2022-03-25 AU AU2022243575A patent/AU2022243575A1/en active Pending
- 2022-03-25 EP EP22723227.9A patent/EP4314831A2/fr active Pending
- 2022-03-25 JP JP2023557047A patent/JP2024511029A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
IL306049A (en) | 2023-11-01 |
CA3213216A1 (fr) | 2022-09-29 |
EP4314831A2 (fr) | 2024-02-07 |
AU2022243575A1 (en) | 2023-11-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7540994B2 (ja) | 高親和性のアイソフォーム選択的TGFβ1阻害剤、およびその使用 | |
US20210340238A1 (en) | TGFß1 INHIBITORS AND USE THEREOF | |
US20230050148A1 (en) | Tgf-beta inhibitors and use thereof | |
US12122823B2 (en) | Isoform-selective TGFB1 inhibitors and use thereof | |
US20230057012A1 (en) | Tgfb inhibitors and use thereof | |
WO2022204581A2 (fr) | Inhibiteurs de tgf-bêta et leur utilisation | |
JP2024511029A (ja) | TGF-β阻害剤及びその使用 | |
EP4348260A2 (fr) | Inhibiteurs de tgf-bêta et leur utilisation thérapeutique | |
US20240294623A1 (en) | Tgf-beta inhibitors and therapeutic use thereof | |
WO2024187051A1 (fr) | Inhibiteurs de tgf-bêta destinés à être utilisés pour traiter un cancer résistant ou réfractaire chez des patients |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231116 |