BR112019014169A2 - Métodos de tratamento de câncer com anticorpos anti-tim-3 - Google Patents

Info

Publication number

BR112019014169A2

BR112019014169A2 BR112019014169-3A BR112019014169A BR112019014169A2 BR 112019014169 A2 BR112019014169 A2 BR 112019014169A2 BR 112019014169 A BR112019014169 A BR 112019014169A BR 112019014169 A2 BR112019014169 A2 BR 112019014169A2

Authority

BR

Brazil

Prior art keywords

cancer

dose

fixed dose

fact

tim

Prior art date

2017-01-09

Links

• Espacenet
• Global Dossier
• Discuss

• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 500
• 201000011510 cancer Diseases 0.000 title claims abstract description 384
• 238000000034 method Methods 0.000 title claims abstract description 353
• 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 title claims description 295
• 238000011282 treatment Methods 0.000 title claims description 91
• 239000011230 binding agent Substances 0.000 claims abstract description 127
• 239000003795 chemical substances by application Substances 0.000 claims description 324
• 239000003112 inhibitor Substances 0.000 claims description 208
• 238000001990 intravenous administration Methods 0.000 claims description 159
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 108
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 108
• 229920001184 polypeptide Polymers 0.000 claims description 105
• 230000035772 mutation Effects 0.000 claims description 87
• 206010014759 Endometrial neoplasm Diseases 0.000 claims description 85
• 206010014733 Endometrial cancer Diseases 0.000 claims description 82
• 238000001802 infusion Methods 0.000 claims description 80
• 108091092878 Microsatellite Proteins 0.000 claims description 71
• 210000004027 cell Anatomy 0.000 claims description 70
• 206010009944 Colon cancer Diseases 0.000 claims description 63
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 60
• 208000020990 adrenal cortex carcinoma Diseases 0.000 claims description 59
• 230000007812 deficiency Effects 0.000 claims description 59
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 57
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 56
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 56
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 54
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 54
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 54
• 206010033128 Ovarian cancer Diseases 0.000 claims description 54
• 201000005202 lung cancer Diseases 0.000 claims description 54
• 208000020816 lung neoplasm Diseases 0.000 claims description 54
• 102100024829 DNA polymerase delta catalytic subunit Human genes 0.000 claims description 52
• 101000909198 Homo sapiens DNA polymerase delta catalytic subunit Proteins 0.000 claims description 52
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 52
• 201000001441 melanoma Diseases 0.000 claims description 52
• 239000012270 PD-1 inhibitor Substances 0.000 claims description 49
• 239000012668 PD-1-inhibitor Substances 0.000 claims description 49
• 229940121655 pd-1 inhibitor Drugs 0.000 claims description 49
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 47
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 47
• 230000027455 binding Effects 0.000 claims description 46
• 230000008439 repair process Effects 0.000 claims description 46
• 206010006187 Breast cancer Diseases 0.000 claims description 45
• 208000026310 Breast neoplasm Diseases 0.000 claims description 44
• 230000008901 benefit Effects 0.000 claims description 43
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 39
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 39
• 208000032818 Microsatellite Instability Diseases 0.000 claims description 38
• 201000010099 disease Diseases 0.000 claims description 37
• 108060003951 Immunoglobulin Proteins 0.000 claims description 36
• 102000018358 immunoglobulin Human genes 0.000 claims description 36
• 230000004044 response Effects 0.000 claims description 35
• 230000001900 immune effect Effects 0.000 claims description 33
• 208000013452 Fallopian tube neoplasm Diseases 0.000 claims description 32
• 150000007523 nucleic acids Chemical class 0.000 claims description 32
• 208000017604 Hodgkin disease Diseases 0.000 claims description 30
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 30
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 30
• 230000034431 double-strand break repair via homologous recombination Effects 0.000 claims description 30
• 206010039491 Sarcoma Diseases 0.000 claims description 29
• 239000000427 antigen Substances 0.000 claims description 29
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 28
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 28
• 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 28
• 108091007433 antigens Proteins 0.000 claims description 28
• 102000036639 antigens Human genes 0.000 claims description 28
• 239000012634 fragment Substances 0.000 claims description 28
• 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 27
• 206010029260 Neuroblastoma Diseases 0.000 claims description 27
• 241000282414 Homo sapiens Species 0.000 claims description 26
• 108090000623 proteins and genes Proteins 0.000 claims description 26
• 201000001342 Fallopian tube cancer Diseases 0.000 claims description 25
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 25
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 25
• 208000026149 Primary peritoneal carcinoma Diseases 0.000 claims description 25
• 206010061289 metastatic neoplasm Diseases 0.000 claims description 25
• 239000007787 solid Substances 0.000 claims description 25
• 201000008968 osteosarcoma Diseases 0.000 claims description 24
• 150000003384 small molecules Chemical group 0.000 claims description 24
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 23
• 208000006168 Ewing Sarcoma Diseases 0.000 claims description 23
• 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 23
• 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 23
• 208000025997 central nervous system neoplasm Diseases 0.000 claims description 23
• 238000002512 chemotherapy Methods 0.000 claims description 23
• 208000028919 diffuse intrinsic pontine glioma Diseases 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 23
• 206010041823 squamous cell carcinoma Diseases 0.000 claims description 23
• 238000002560 therapeutic procedure Methods 0.000 claims description 23
• 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 23
• 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 22
• 229940127121 immunoconjugate Drugs 0.000 claims description 21
• 102000039446 nucleic acids Human genes 0.000 claims description 19
• 108020004707 nucleic acids Proteins 0.000 claims description 19
• 108010074708 B7-H1 Antigen Proteins 0.000 claims description 18
• 229940045513 CTLA4 antagonist Drugs 0.000 claims description 18
• 206010008342 Cervix carcinoma Diseases 0.000 claims description 18
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 18
• 201000010881 cervical cancer Diseases 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 18
• 108020004414 DNA Proteins 0.000 claims description 17
• 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 claims description 17
• 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 claims description 16
• 229940125563 LAG3 inhibitor Drugs 0.000 claims description 16
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 16
• 150000001720 carbohydrates Chemical class 0.000 claims description 16
• 206010017758 gastric cancer Diseases 0.000 claims description 16
• 238000009169 immunotherapy Methods 0.000 claims description 16
• 201000011549 stomach cancer Diseases 0.000 claims description 16
• 210000001215 vagina Anatomy 0.000 claims description 16
• 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 description 15
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 15
• 208000008383 Wilms tumor Diseases 0.000 claims description 15
• 150000002632 lipids Chemical class 0.000 claims description 15
• PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib Chemical compound N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 claims description 15
• 229950011068 niraparib Drugs 0.000 claims description 15
• 238000001959 radiotherapy Methods 0.000 claims description 15
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 14
• 206010038389 Renal cancer Diseases 0.000 claims description 14
• 201000010982 kidney cancer Diseases 0.000 claims description 14
• 229910052751 metal Inorganic materials 0.000 claims description 14
• 239000002184 metal Substances 0.000 claims description 14
• 102000004169 proteins and genes Human genes 0.000 claims description 14
• 230000011664 signaling Effects 0.000 claims description 14
• 239000003053 toxin Substances 0.000 claims description 14
• 231100000765 toxin Toxicity 0.000 claims description 14
• 238000011277 treatment modality Methods 0.000 claims description 14
• 206010005003 Bladder cancer Diseases 0.000 claims description 13
• 239000012661 PARP inhibitor Substances 0.000 claims description 13
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims description 13
• 206010060862 Prostate cancer Diseases 0.000 claims description 13
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 13
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 13
• 230000002489 hematologic effect Effects 0.000 claims description 13
• 230000028993 immune response Effects 0.000 claims description 13
• 230000005764 inhibitory process Effects 0.000 claims description 13
• 229940124597 therapeutic agent Drugs 0.000 claims description 13
• 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims description 12
• 208000014018 liver neoplasm Diseases 0.000 claims description 12
• 230000036961 partial effect Effects 0.000 claims description 12
• 238000001356 surgical procedure Methods 0.000 claims description 12
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 12
• 239000012275 CTLA-4 inhibitor Substances 0.000 claims description 11
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 11
• 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 11
• 210000000436 anus Anatomy 0.000 claims description 11
• 230000000694 effects Effects 0.000 claims description 11
• 201000004101 esophageal cancer Diseases 0.000 claims description 11
• 201000010536 head and neck cancer Diseases 0.000 claims description 11
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 10
• 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 10
• -1 JPI 289 Chemical compound 0.000 claims description 9
• 208000002030 Merkel cell carcinoma Diseases 0.000 claims description 9
• 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 claims description 9
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 9
• 206010041848 Squamous cell carcinoma of the cervix Diseases 0.000 claims description 9
• 208000032249 Squamous cell carcinoma of the penis Diseases 0.000 claims description 9
• 206010041875 Squamous cell carcinoma of the vulva Diseases 0.000 claims description 9
• 229940125555 TIGIT inhibitor Drugs 0.000 claims description 9
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 9
• 208000025337 Vulvar squamous cell carcinoma Diseases 0.000 claims description 9
• 201000006612 cervical squamous cell carcinoma Diseases 0.000 claims description 9
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 9
• 210000002865 immune cell Anatomy 0.000 claims description 9
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 9
• 201000002528 pancreatic cancer Diseases 0.000 claims description 9
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 9
• 208000021333 squamous cell carcinoma of penis Diseases 0.000 claims description 9
• 206010073358 Anal squamous cell carcinoma Diseases 0.000 claims description 8
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 8
• 206010041866 Squamous cell carcinoma of the vagina Diseases 0.000 claims description 8
• 238000011374 additional therapy Methods 0.000 claims description 8
• 208000029742 colonic neoplasm Diseases 0.000 claims description 8
• 230000002950 deficient Effects 0.000 claims description 8
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 8
• 206010046766 uterine cancer Diseases 0.000 claims description 8
• 208000021153 vaginal squamous cell carcinoma Diseases 0.000 claims description 8
• 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 7
• 208000034578 Multiple myelomas Diseases 0.000 claims description 7
• 208000024770 Thyroid neoplasm Diseases 0.000 claims description 7
• 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 7
• 208000009956 adenocarcinoma Diseases 0.000 claims description 7
• 208000032839 leukemia Diseases 0.000 claims description 7
• 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 7
• HMABYWSNWIZPAG-UHFFFAOYSA-N rucaparib Chemical compound C1=CC(CNC)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC(F)=C3 HMABYWSNWIZPAG-UHFFFAOYSA-N 0.000 claims description 7
• 229950004707 rucaparib Drugs 0.000 claims description 7
• 206010044412 transitional cell carcinoma Diseases 0.000 claims description 7
• 201000005102 vulva cancer Diseases 0.000 claims description 7
• 206010073360 Appendix cancer Diseases 0.000 claims description 6
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 6
• 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 6
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 6
• 208000006265 Renal cell carcinoma Diseases 0.000 claims description 6
• 208000007128 adrenocortical carcinoma Diseases 0.000 claims description 6
• 208000021780 appendiceal neoplasm Diseases 0.000 claims description 6
• 230000007547 defect Effects 0.000 claims description 6
• 238000011156 evaluation Methods 0.000 claims description 6
• 201000007270 liver cancer Diseases 0.000 claims description 6
• 208000008732 thymoma Diseases 0.000 claims description 6
• 201000002510 thyroid cancer Diseases 0.000 claims description 6
• 208000025444 tumor of salivary gland Diseases 0.000 claims description 6
• 206010046885 vaginal cancer Diseases 0.000 claims description 6
• 208000013139 vaginal neoplasm Diseases 0.000 claims description 6
• 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 5
• 206010023825 Laryngeal cancer Diseases 0.000 claims description 5
• 208000018142 Leiomyosarcoma Diseases 0.000 claims description 5
• 206010027406 Mesothelioma Diseases 0.000 claims description 5
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims description 5
• 206010061934 Salivary gland cancer Diseases 0.000 claims description 5
• 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
• HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 claims description 5
• 230000034994 death Effects 0.000 claims description 5
• 231100000517 death Toxicity 0.000 claims description 5
• 239000012636 effector Substances 0.000 claims description 5
• 201000010175 gallbladder cancer Diseases 0.000 claims description 5
• 206010023841 laryngeal neoplasm Diseases 0.000 claims description 5
• 201000008026 nephroblastoma Diseases 0.000 claims description 5
• FDLYAMZZIXQODN-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FDLYAMZZIXQODN-UHFFFAOYSA-N 0.000 claims description 5
• 238000012163 sequencing technique Methods 0.000 claims description 5
• JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 claims description 5
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 4
• 108060002716 Exonuclease Proteins 0.000 claims description 4
• 208000024313 Testicular Neoplasms Diseases 0.000 claims description 4
• 206010057644 Testis cancer Diseases 0.000 claims description 4
• 102000013165 exonuclease Human genes 0.000 claims description 4
• 210000004602 germ cell Anatomy 0.000 claims description 4
• 201000005249 lung adenocarcinoma Diseases 0.000 claims description 4
• 229960003301 nivolumab Drugs 0.000 claims description 4
• 229960000572 olaparib Drugs 0.000 claims description 4
• 229960002621 pembrolizumab Drugs 0.000 claims description 4
• 229950004550 talazoparib Drugs 0.000 claims description 4
• 201000003120 testicular cancer Diseases 0.000 claims description 4
• 229950011257 veliparib Drugs 0.000 claims description 4
• 102000010567 DNA Polymerase II Human genes 0.000 claims description 3
• 108010063113 DNA Polymerase II Proteins 0.000 claims description 3
• 108010071146 DNA Polymerase III Proteins 0.000 claims description 3
• 102000007528 DNA Polymerase III Human genes 0.000 claims description 3
• 208000037913 T-cell disorder Diseases 0.000 claims description 3
• 229960003852 atezolizumab Drugs 0.000 claims description 3
• 229950002916 avelumab Drugs 0.000 claims description 3
• 229950007712 camrelizumab Drugs 0.000 claims description 3
• 229940121420 cemiplimab Drugs 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 229950009791 durvalumab Drugs 0.000 claims description 3
• 208000005017 glioblastoma Diseases 0.000 claims description 3
• 201000004962 larynx cancer Diseases 0.000 claims description 3
• 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 claims description 3
• 150000003839 salts Chemical class 0.000 claims description 3
• 229940121497 sintilimab Drugs 0.000 claims description 3
• 229950007123 tislelizumab Drugs 0.000 claims description 3
• DENYZIUJOTUUNY-MRXNPFEDSA-N (2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one Chemical compound FC=1C=C2C=3C=4C(CN5[C@@](C4NC3C1)(CCC5)C)=NNC2=O DENYZIUJOTUUNY-MRXNPFEDSA-N 0.000 claims description 2
• CTLOSZHDGZLOQE-UHFFFAOYSA-N 14-methoxy-9-[(4-methylpiperazin-1-yl)methyl]-9,19-diazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),2(6),7(11),13(18),14,16-hexaene-8,10-dione Chemical compound O=C1C2=C3C=4C(OC)=CC=CC=4NC3=C3CCCC3=C2C(=O)N1CN1CCN(C)CC1 CTLOSZHDGZLOQE-UHFFFAOYSA-N 0.000 claims description 2
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims description 2
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 2
• HRYKZAKEAVZGJD-UHFFFAOYSA-N 2-methyl-3,5,7,8-tetrahydro-4h-thiopyrano[4,3-d]pyrimidin-4-one Chemical compound C1CSCC2=C1N=C(C)NC2=O HRYKZAKEAVZGJD-UHFFFAOYSA-N 0.000 claims description 2
• GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 claims description 2
• HYNBNUYQTQIHJK-UHFFFAOYSA-N 4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CC(OC)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F HYNBNUYQTQIHJK-UHFFFAOYSA-N 0.000 claims description 2
• XJGXCBHXFWBOTN-UHFFFAOYSA-N 4-[[4-fluoro-3-[2-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1CN2N=C(C(F)(F)F)N=C2CN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F XJGXCBHXFWBOTN-UHFFFAOYSA-N 0.000 claims description 2
• QNQFPYADHVFRKQ-UHFFFAOYSA-N 4-[[4-fluoro-3-[5-methyl-3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2h-phthalazin-1-one Chemical compound C1=CC=C2C(CC=3C=C(C(=CC=3)F)C(=O)N3CC(N4C(=NN=C4C3)C(F)(F)F)C)=NNC(=O)C2=C1 QNQFPYADHVFRKQ-UHFFFAOYSA-N 0.000 claims description 2
• GRPXLKXGJAGYSD-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NC=C(C#N)C=C1 GRPXLKXGJAGYSD-UHFFFAOYSA-N 0.000 claims description 2
• JLFSBHQQXIAQEC-UHFFFAOYSA-N 9x5a2qia7c Chemical compound C1=CC(C(=O)NN2)=C3C2=NC(CN2CC4=CC=CC=C4C2)=NC3=C1 JLFSBHQQXIAQEC-UHFFFAOYSA-N 0.000 claims description 2
• 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
• 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 claims description 2
• 230000006044 T cell activation Effects 0.000 claims description 2
• 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 2
• 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
• 230000036755 cellular response Effects 0.000 claims description 2
• BWVHYDYUKQEFHG-UHFFFAOYSA-N cep-8983 Chemical compound COC1=CC=CC2=C1C1=C3C(=O)NC(=O)C3=C3CCCC3=C1N2 BWVHYDYUKQEFHG-UHFFFAOYSA-N 0.000 claims description 2
• 231100000433 cytotoxic Toxicity 0.000 claims description 2
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 2
• 230000001472 cytotoxic effect Effects 0.000 claims description 2
• 230000028996 humoral immune response Effects 0.000 claims description 2
• 230000021633 leukocyte mediated immunity Effects 0.000 claims description 2
• HAVFFEMDLROBGI-UHFFFAOYSA-N m8926c7ilx Chemical compound C1CC(O)CCN1CC1=CC=C(OC=2C3=C(C(NN=C33)=O)C=CC=2)C3=C1 HAVFFEMDLROBGI-UHFFFAOYSA-N 0.000 claims description 2
• ISGGVCWFTPTHIX-UHFFFAOYSA-N n'-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidamide;dihydrochloride Chemical compound Cl.Cl.C1CCCCN1CC(O)CONC(=N)C1=CC=CN=C1 ISGGVCWFTPTHIX-UHFFFAOYSA-N 0.000 claims description 2
• 125000003275 alpha amino acid group Chemical group 0.000 claims 6
• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims 5
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims 5
• 102000008096 B7-H1 Antigen Human genes 0.000 claims 4
• 102000008203 CTLA-4 Antigen Human genes 0.000 claims 4
• 102000007295 Mucin-3 Human genes 0.000 claims 3
• 108010008701 Mucin-3 Proteins 0.000 claims 3
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims 2
• 230000005867 T cell response Effects 0.000 claims 1
• 201000003761 Vaginal carcinoma Diseases 0.000 claims 1
• 230000002708 enhancing effect Effects 0.000 claims 1
• 230000001939 inductive effect Effects 0.000 claims 1
• 230000009467 reduction Effects 0.000 claims 1
• INBJJAFXHQQSRW-STOWLHSFSA-N rucaparib camsylate Chemical compound CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.CNCc1ccc(cc1)-c1[nH]c2cc(F)cc3C(=O)NCCc1c23 INBJJAFXHQQSRW-STOWLHSFSA-N 0.000 claims 1
• 201000002314 small intestine cancer Diseases 0.000 claims 1
• 230000004565 tumor cell growth Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 79
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 abstract description 3
• 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 abstract 2
• 150000001413 amino acids Chemical group 0.000 description 102
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 74
• 238000002648 combination therapy Methods 0.000 description 22
• 230000014509 gene expression Effects 0.000 description 22
• 230000001394 metastastic effect Effects 0.000 description 20
• 230000003902 lesion Effects 0.000 description 18
• 210000003679 cervix uteri Anatomy 0.000 description 16
• 229920001542 oligosaccharide Polymers 0.000 description 16
• 150000002482 oligosaccharides Chemical class 0.000 description 16
• 210000003899 penis Anatomy 0.000 description 16
• 238000009097 single-agent therapy Methods 0.000 description 16
• 210000003905 vulva Anatomy 0.000 description 16
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 15
• 208000026144 diffuse midline glioma, H3 K27M-mutant Diseases 0.000 description 15
• 201000009030 Carcinoma Diseases 0.000 description 14
• 241001465754 Metazoa Species 0.000 description 14
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
• 108010076504 Protein Sorting Signals Proteins 0.000 description 12
• 239000002773 nucleotide Substances 0.000 description 12
• 235000001014 amino acid Nutrition 0.000 description 11
• 208000037218 exstrophy-epispadias complex Diseases 0.000 description 11
• 230000003993 interaction Effects 0.000 description 11
• 230000001225 therapeutic effect Effects 0.000 description 11
• 229940024606 amino acid Drugs 0.000 description 10
• 150000004676 glycans Chemical class 0.000 description 10
• 208000037819 metastatic cancer Diseases 0.000 description 10
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 10
• 125000003729 nucleotide group Chemical group 0.000 description 10
• 210000001672 ovary Anatomy 0.000 description 10
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 235000014633 carbohydrates Nutrition 0.000 description 9
• 201000003444 follicular lymphoma Diseases 0.000 description 9
• 210000004072 lung Anatomy 0.000 description 9
• 210000003101 oviduct Anatomy 0.000 description 9
• 230000004083 survival effect Effects 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 8
• 206010025323 Lymphomas Diseases 0.000 description 8
• 150000001875 compounds Chemical class 0.000 description 8
• 238000010494 dissociation reaction Methods 0.000 description 8
• 230000005593 dissociations Effects 0.000 description 8
• 210000004962 mammalian cell Anatomy 0.000 description 8
• 208000037821 progressive disease Diseases 0.000 description 8
• 235000018102 proteins Nutrition 0.000 description 8
• 208000004548 serous cystadenocarcinoma Diseases 0.000 description 8
• 208000000587 small cell lung carcinoma Diseases 0.000 description 8
• 230000004614 tumor growth Effects 0.000 description 8
• 239000013598 vector Substances 0.000 description 8
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 7
• 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 7
• 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 7
• 206010041067 Small cell lung cancer Diseases 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 201000001343 fallopian tube carcinoma Diseases 0.000 description 7
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 7
• 229910052697 platinum Inorganic materials 0.000 description 7
• 241000894007 species Species 0.000 description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• 102000015728 Mucins Human genes 0.000 description 6
• 108010063954 Mucins Proteins 0.000 description 6
• 241000699666 Mus <mouse, genus> Species 0.000 description 6
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
• 230000013595 glycosylation Effects 0.000 description 6
• 238000006206 glycosylation reaction Methods 0.000 description 6
• 230000004048 modification Effects 0.000 description 6
• 238000012986 modification Methods 0.000 description 6
• 201000002628 peritoneum cancer Diseases 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 230000000306 recurrent effect Effects 0.000 description 6
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 5
• 208000003174 Brain Neoplasms Diseases 0.000 description 5
• 102000003886 Glycoproteins Human genes 0.000 description 5
• 108090000288 Glycoproteins Proteins 0.000 description 5
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
• 102000017578 LAG3 Human genes 0.000 description 5
• 101150030213 Lag3 gene Proteins 0.000 description 5
• 241000283973 Oryctolagus cuniculus Species 0.000 description 5
• 238000010521 absorption reaction Methods 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 5
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 5
• 229940011871 estrogen Drugs 0.000 description 5
• 239000000262 estrogen Substances 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 238000003364 immunohistochemistry Methods 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 230000000869 mutational effect Effects 0.000 description 5
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical group FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 5
• 238000007911 parenteral administration Methods 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 238000011285 therapeutic regimen Methods 0.000 description 5
• 230000000699 topical effect Effects 0.000 description 5
• 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 5
• 210000004291 uterus Anatomy 0.000 description 5
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 208000023275 Autoimmune disease Diseases 0.000 description 4
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
• 208000006332 Choriocarcinoma Diseases 0.000 description 4
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
• 101000961149 Homo sapiens Immunoglobulin heavy constant gamma 4 Proteins 0.000 description 4
• 101000840257 Homo sapiens Immunoglobulin kappa constant Proteins 0.000 description 4
• 102100029572 Immunoglobulin kappa constant Human genes 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
• 241000699670 Mus sp. Species 0.000 description 4
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• 241000288906 Primates Species 0.000 description 4
• 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 4
• 206010047741 Vulval cancer Diseases 0.000 description 4
• 239000003242 anti bacterial agent Substances 0.000 description 4
• 230000001934 delay Effects 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 230000003211 malignant effect Effects 0.000 description 4
• 210000000214 mouth Anatomy 0.000 description 4
• 208000025113 myeloid leukemia Diseases 0.000 description 4
• 238000007481 next generation sequencing Methods 0.000 description 4
• 239000008194 pharmaceutical composition Substances 0.000 description 4
• 238000011518 platinum-based chemotherapy Methods 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 210000000813 small intestine Anatomy 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 239000000243 solution Substances 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 230000009870 specific binding Effects 0.000 description 4
• 230000006641 stabilisation Effects 0.000 description 4
• 238000011105 stabilization Methods 0.000 description 4
• 238000007920 subcutaneous administration Methods 0.000 description 4
• 210000004881 tumor cell Anatomy 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• 206010061424 Anal cancer Diseases 0.000 description 3
• 208000007860 Anus Neoplasms Diseases 0.000 description 3
• 206010003571 Astrocytoma Diseases 0.000 description 3
• 108700020463 BRCA1 Proteins 0.000 description 3
• 101150072950 BRCA1 gene Proteins 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 102100025401 Breast cancer type 1 susceptibility protein Human genes 0.000 description 3
• 208000035473 Communicable disease Diseases 0.000 description 3
• 241000699802 Cricetulus griseus Species 0.000 description 3
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 3
• 206010061818 Disease progression Diseases 0.000 description 3
• 102100031351 Galectin-9 Human genes 0.000 description 3
• 101710121810 Galectin-9 Proteins 0.000 description 3
• 241000711549 Hepacivirus C Species 0.000 description 3
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
• 241000725303 Human immunodeficiency virus Species 0.000 description 3
• 102100039347 Immunoglobulin heavy constant gamma 4 Human genes 0.000 description 3
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
• 108091081062 Repeated sequence (DNA) Proteins 0.000 description 3
• 244000000231 Sesamum indicum Species 0.000 description 3
• 208000000453 Skin Neoplasms Diseases 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 3
• 201000005969 Uveal melanoma Diseases 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 201000011165 anus cancer Diseases 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 238000004422 calculation algorithm Methods 0.000 description 3
• 230000002596 correlated effect Effects 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• 210000004443 dendritic cell Anatomy 0.000 description 3
• 230000005750 disease progression Effects 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 239000002612 dispersion medium Substances 0.000 description 3
• 230000002357 endometrial effect Effects 0.000 description 3
• 208000037828 epithelial carcinoma Diseases 0.000 description 3
• 210000003238 esophagus Anatomy 0.000 description 3
• 210000004996 female reproductive system Anatomy 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 230000004927 fusion Effects 0.000 description 3
• 210000004907 gland Anatomy 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 208000003747 lymphoid leukemia Diseases 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 201000000050 myeloid neoplasm Diseases 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000004393 prognosis Methods 0.000 description 3
• 230000002035 prolonged effect Effects 0.000 description 3
• 210000003728 serous cell Anatomy 0.000 description 3
• 201000000849 skin cancer Diseases 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• 206010000830 Acute leukaemia Diseases 0.000 description 2
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 2
• 208000003200 Adenoma Diseases 0.000 description 2
• 108091023037 Aptamer Proteins 0.000 description 2
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 2
• 206010005949 Bone cancer Diseases 0.000 description 2
• 208000018084 Bone neoplasm Diseases 0.000 description 2
• 206010055113 Breast cancer metastatic Diseases 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• 241000251730 Chondrichthyes Species 0.000 description 2
• 206010052358 Colorectal cancer metastatic Diseases 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 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
• 208000005431 Endometrioid Carcinoma Diseases 0.000 description 2
• 102100038595 Estrogen receptor Human genes 0.000 description 2
• 108010008177 Fd immunoglobulins Proteins 0.000 description 2
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
• 208000017891 HER2 positive breast carcinoma Diseases 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 description 2
• 101000955999 Homo sapiens V-set domain-containing T-cell activation inhibitor 1 Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 208000000172 Medulloblastoma Diseases 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
• 208000003445 Mouth Neoplasms Diseases 0.000 description 2
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
• 108091028043 Nucleic acid sequence Proteins 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 241000725643 Respiratory syncytial virus Species 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 2
• 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 2
• 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 2
• 208000014070 Vestibular schwannoma Diseases 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 208000004064 acoustic neuroma Diseases 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 208000037842 advanced-stage tumor Diseases 0.000 description 2
• 230000003042 antagnostic effect Effects 0.000 description 2
• 230000003466 anti-cipated effect Effects 0.000 description 2
• 239000003443 antiviral agent Substances 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
• 230000000712 assembly Effects 0.000 description 2
• 238000000429 assembly Methods 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 210000000013 bile duct Anatomy 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 150000005829 chemical entities Chemical class 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 201000010897 colon adenocarcinoma Diseases 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 238000000375 direct analysis in real time Methods 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000012063 dual-affinity re-targeting Methods 0.000 description 2
• 108010011867 ecallantide Proteins 0.000 description 2
• 210000004696 endometrium Anatomy 0.000 description 2
• 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 2
• 108010038795 estrogen receptors Proteins 0.000 description 2
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 239000007951 isotonicity adjuster Substances 0.000 description 2
• VBGWSQKGUZHFPS-VGMMZINCSA-N kalbitor Chemical compound C([C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N[C@H](C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)NCC(=O)NCC(=O)N[C@H]3CSSC[C@H](NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CO)NC(=O)[C@H](CC=4NC=NC=4)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O)CSSC[C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC3=O)CSSC2)C(=O)N[C@@H]([C@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N1)[C@@H](C)CC)[C@H](C)O)=O)[C@@H](C)CC)C1=CC=CC=C1 VBGWSQKGUZHFPS-VGMMZINCSA-N 0.000 description 2
• 229940018902 kalbitor Drugs 0.000 description 2
• 210000000867 larynx Anatomy 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 2
• 230000000527 lymphocytic effect Effects 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 206010027191 meningioma Diseases 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 208000021039 metastatic melanoma Diseases 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 201000004228 ovarian endometrial cancer Diseases 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 102000003998 progesterone receptors Human genes 0.000 description 2
• 108090000468 progesterone receptors Proteins 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 231100000205 reproductive and developmental toxicity Toxicity 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 239000008174 sterile solution Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 150000005846 sugar alcohols Polymers 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 210000001685 thyroid gland Anatomy 0.000 description 2
• 230000005945 translocation Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• AMGNHZVUZWILSB-UHFFFAOYSA-N 1,2-bis(2-chloroethylsulfanyl)ethane Chemical compound ClCCSCCSCCCl AMGNHZVUZWILSB-UHFFFAOYSA-N 0.000 description 1
• GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical class OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
• SRNWOUGRCWSEMX-TYASJMOZSA-N ADP-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1OC(O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-TYASJMOZSA-N 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
• 206010001233 Adenoma benign Diseases 0.000 description 1
• 101150051188 Adora2a gene Proteins 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 108050001427 Avidin/streptavidin Proteins 0.000 description 1
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 229940125565 BMS-986016 Drugs 0.000 description 1
• 229940125557 BMS-986207 Drugs 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 206010004593 Bile duct cancer Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 102100024263 CD160 antigen Human genes 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 108010062802 CD66 antigens Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
• 108010072135 Cell Adhesion Molecule-1 Proteins 0.000 description 1
• 102100024649 Cell adhesion molecule 1 Human genes 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 241000938605 Crocodylia Species 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 241000725619 Dengue virus Species 0.000 description 1
• 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000021309 Germ cell tumor Diseases 0.000 description 1
• 201000010915 Glioblastoma multiforme 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
• 206010060980 Granular cell tumour Diseases 0.000 description 1
• 208000005234 Granulosa Cell Tumor Diseases 0.000 description 1
• 108700010013 HMGB1 Proteins 0.000 description 1
• 101150021904 HMGB1 gene Proteins 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
• 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 description 1
• 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 208000008051 Hereditary Nonpolyposis Colorectal Neoplasms Diseases 0.000 description 1
• 206010051922 Hereditary non-polyposis colorectal cancer syndrome Diseases 0.000 description 1
• 102100037907 High mobility group protein B1 Human genes 0.000 description 1
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
• 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 1
• 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
• 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 1
• 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
• 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 102100037850 Interferon gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 206010061252 Intraocular melanoma Diseases 0.000 description 1
• 108010043610 KIR Receptors Proteins 0.000 description 1
• 108090001090 Lectins Proteins 0.000 description 1
• 102000004856 Lectins Human genes 0.000 description 1
• 206010024305 Leukaemia monocytic Diseases 0.000 description 1
• 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 1
• 206010050017 Lung cancer metastatic Diseases 0.000 description 1
• 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
• 201000005027 Lynch syndrome Diseases 0.000 description 1
• 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 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
• 102000043131 MHC class II family Human genes 0.000 description 1
• 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
• 208000007054 Medullary Carcinoma Diseases 0.000 description 1
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
• 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 208000010505 Nose Neoplasms Diseases 0.000 description 1
• 201000010133 Oligodendroglioma Diseases 0.000 description 1
• 206010033264 Ovarian hyperfunction Diseases 0.000 description 1
• 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 208000002151 Pleural effusion Diseases 0.000 description 1
• 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
• 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038111 Recurrent cancer Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 108010008038 Synthetic Vaccines Proteins 0.000 description 1
• 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
• 210000000447 Th1 cell Anatomy 0.000 description 1
• 210000000068 Th17 cell Anatomy 0.000 description 1
• 206010043515 Throat cancer Diseases 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
• 206010046788 Uterine haemorrhage Diseases 0.000 description 1
• 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 1
• 206010046910 Vaginal haemorrhage Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 229940123627 Viral replication inhibitor Drugs 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 208000017733 acquired polycythemia vera Diseases 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 208000037831 acute erythroleukemic leukemia Diseases 0.000 description 1
• 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
• 208000036676 acute undifferentiated leukemia Diseases 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 206010002224 anaplastic astrocytoma Diseases 0.000 description 1
• 230000002547 anomalous effect Effects 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000003833 bile salt Substances 0.000 description 1
• 229940093761 bile salts Drugs 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 201000001531 bladder carcinoma Diseases 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000009766 cell sprouting Effects 0.000 description 1
• 230000010307 cell transformation Effects 0.000 description 1
• 201000007455 central nervous system cancer Diseases 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 208000013056 classic Hodgkin lymphoma Diseases 0.000 description 1
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 210000001608 connective tissue cell Anatomy 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 208000030381 cutaneous melanoma Diseases 0.000 description 1
• 208000031513 cyst Diseases 0.000 description 1
• 208000002445 cystadenocarcinoma Diseases 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 210000004207 dermis Anatomy 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 108020001096 dihydrofolate reductase Proteins 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 210000001840 diploid cell Anatomy 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 229940126534 drug product Drugs 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000002497 edematous effect Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 229940056913 eftilagimod alfa Drugs 0.000 description 1
• 210000000750 endocrine system Anatomy 0.000 description 1
• 201000003908 endometrial adenocarcinoma Diseases 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 201000006828 endometrial hyperplasia Diseases 0.000 description 1
• 208000028730 endometrioid adenocarcinoma Diseases 0.000 description 1
• 208000023965 endometrium neoplasm Diseases 0.000 description 1
• 238000001839 endoscopy Methods 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 201000006564 estrogen excess Diseases 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 201000010255 female reproductive organ cancer Diseases 0.000 description 1
• 210000005002 female reproductive tract Anatomy 0.000 description 1
• 230000003176 fibrotic effect Effects 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
• MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
• 229960002714 fluticasone Drugs 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 201000006604 granular cell tumor Diseases 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000007773 growth pattern Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000025750 heavy chain disease Diseases 0.000 description 1
• 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 208000005252 hepatitis A Diseases 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 230000000642 iatrogenic effect Effects 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 229940121569 ieramilimab Drugs 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 208000020082 intraepithelial neoplasia Diseases 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000007914 intraventricular administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 239000002523 lectin Substances 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 238000000786 liquid-assisted grinding Methods 0.000 description 1
• 229940124590 live attenuated vaccine Drugs 0.000 description 1
• 229940023012 live-attenuated vaccine Drugs 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 208000012804 lymphangiosarcoma Diseases 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 238000001471 micro-filtration Methods 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 201000006894 monocytic leukemia Diseases 0.000 description 1
• 208000001611 myxosarcoma Diseases 0.000 description 1
• IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 208000037830 nasal cancer Diseases 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000006218 nasal suppository Substances 0.000 description 1
• 210000001989 nasopharynx Anatomy 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 210000003757 neuroblast Anatomy 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 230000000683 nonmetastatic effect Effects 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
• 201000010198 papillary carcinoma Diseases 0.000 description 1
• 208000003154 papilloma Diseases 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 210000002990 parathyroid gland Anatomy 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000004303 peritoneum Anatomy 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• 230000010399 physical interaction Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 210000004560 pineal gland Anatomy 0.000 description 1
• 230000001817 pituitary effect Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 208000037244 polycythemia vera Diseases 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 210000001586 pre-b-lymphocyte Anatomy 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 238000012207 quantitative assay Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 210000004994 reproductive system Anatomy 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 201000003708 skin melanoma Diseases 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 208000037959 spinal tumor Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000013517 stratification Methods 0.000 description 1
• 229940031626 subunit vaccine Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 210000004243 sweat Anatomy 0.000 description 1
• 201000010965 sweat gland carcinoma Diseases 0.000 description 1
• 206010042863 synovial sarcoma Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 210000001138 tear Anatomy 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 210000001541 thymus gland Anatomy 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 229950007217 tremelimumab Drugs 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 229960005486 vaccine Drugs 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 238000009777 vacuum freeze-drying Methods 0.000 description 1
• 229940126580 vector vaccine Drugs 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 239000012905 visible particle Substances 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 229940055760 yervoy Drugs 0.000 description 1