IL297395B2 - Agonists for BTLA fusion proteins and uses thereof - Google Patents

Info

Publication number

IL297395B2

IL297395B2 IL297395A IL29739522A IL297395B2 IL 297395 B2 IL297395 B2 IL 297395B2 IL 297395 A IL297395 A IL 297395A IL 29739522 A IL29739522 A IL 29739522A IL 297395 B2 IL297395 B2 IL 297395B2

Authority

IL

Israel

Prior art keywords

hvem

protein

btla

fusion protein

cells

Prior art date

2015-06-30

Links

• Espacenet
• Global Dossier
• Discuss

• 108020001507 fusion proteins Proteins 0.000 title claims description 127
• 102000037865 fusion proteins Human genes 0.000 title claims description 126
• 229940076376 protein agonist Drugs 0.000 title description 2
• 101150025010 Btla gene Proteins 0.000 title 1
• 102000012220 Member 14 Tumor Necrosis Factor Receptors Human genes 0.000 claims description 248
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 248
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 199
• 102220031963 rs431825178 Human genes 0.000 claims description 134
• 102220475086 Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6_L90A_mutation Human genes 0.000 claims description 114
• 108090000623 proteins and genes Proteins 0.000 claims description 113
• 102000004169 proteins and genes Human genes 0.000 claims description 110
• 230000035772 mutation Effects 0.000 claims description 87
• 102200112077 rs747956857 Human genes 0.000 claims description 81
• 206010028980 Neoplasm Diseases 0.000 claims description 47
• -1 41BBL Proteins 0.000 claims description 44
• 230000026731 phosphorylation Effects 0.000 claims description 40
• 238000006366 phosphorylation reaction Methods 0.000 claims description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
• 201000011510 cancer Diseases 0.000 claims description 28
• 230000028993 immune response Effects 0.000 claims description 28
• 208000035475 disorder Diseases 0.000 claims description 22
• 108010002350 Interleukin-2 Proteins 0.000 claims description 21
• 102000000588 Interleukin-2 Human genes 0.000 claims description 21
• 229960004641 rituximab Drugs 0.000 claims description 19
• 229940122494 BTLA agonist Drugs 0.000 claims description 18
• 208000023275 Autoimmune disease Diseases 0.000 claims description 17
• 230000001413 cellular effect Effects 0.000 claims description 17
• 230000002829 reductive effect Effects 0.000 claims description 15
• 102000019149 MAP kinase activity proteins Human genes 0.000 claims description 14
• 108040008097 MAP kinase activity proteins Proteins 0.000 claims description 14
• 102100040247 Tumor necrosis factor Human genes 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 13
• 150000001413 amino acids Chemical class 0.000 claims description 13
• 102000004127 Cytokines Human genes 0.000 claims description 12
• 108090000695 Cytokines Proteins 0.000 claims description 12
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 12
• 229960000548 alemtuzumab Drugs 0.000 claims description 12
• 229960005027 natalizumab Drugs 0.000 claims description 12
• 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 claims description 10
• 239000002246 antineoplastic agent Substances 0.000 claims description 10
• 229940127089 cytotoxic agent Drugs 0.000 claims description 10
• 102000052793 human TNFRSF14 Human genes 0.000 claims description 10
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
• RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 claims description 8
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
• 108010005716 Interferon beta-1a Proteins 0.000 claims description 8
• GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims description 8
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 8
• 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 claims description 8
• 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 claims description 8
• 229960002964 adalimumab Drugs 0.000 claims description 8
• 229960000556 fingolimod Drugs 0.000 claims description 8
• KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims description 8
• 229940048921 humira Drugs 0.000 claims description 8
• 229960001001 ibritumomab tiuxetan Drugs 0.000 claims description 8
• 229960000598 infliximab Drugs 0.000 claims description 8
• 229940116176 remicade Drugs 0.000 claims description 8
• UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 claims description 8
• 229960003989 tocilizumab Drugs 0.000 claims description 8
• 229960005267 tositumomab Drugs 0.000 claims description 8
• 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 8
• 229940079023 tysabri Drugs 0.000 claims description 8
• 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 claims description 7
• 108010050904 Interferons Proteins 0.000 claims description 7
• 102000014150 Interferons Human genes 0.000 claims description 7
• 102100033461 Interleukin-17A Human genes 0.000 claims description 7
• 229960003115 certolizumab pegol Drugs 0.000 claims description 7
• 108010002586 Interleukin-7 Proteins 0.000 claims description 6
• 125000000539 amino acid group Chemical group 0.000 claims description 6
• 102100037354 Ectodysplasin-A Human genes 0.000 claims description 5
• 108010008165 Etanercept Proteins 0.000 claims description 5
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 5
• 101000880080 Homo sapiens Ectodysplasin-A Proteins 0.000 claims description 5
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 5
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 5
• 108010076504 Protein Sorting Signals Proteins 0.000 claims description 5
• 108700012411 TNFSF10 Proteins 0.000 claims description 5
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 208000024908 graft versus host disease Diseases 0.000 claims description 5
• 210000004185 liver Anatomy 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 210000003491 skin Anatomy 0.000 claims description 5
• 210000004872 soft tissue Anatomy 0.000 claims description 5
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 4
• BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims description 4
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 4
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 4
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 4
• WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 4
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 4
• 208000026872 Addison Disease Diseases 0.000 claims description 4
• 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 4
• 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 4
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 4
• 208000023328 Basedow disease Diseases 0.000 claims description 4
• 108010006654 Bleomycin Proteins 0.000 claims description 4
• 102100032367 C-C motif chemokine 5 Human genes 0.000 claims description 4
• 102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims description 4
• 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 4
• 108010046080 CD27 Ligand Proteins 0.000 claims description 4
• 102100027207 CD27 antigen Human genes 0.000 claims description 4
• 108010029697 CD40 Ligand Proteins 0.000 claims description 4
• 101150013553 CD40 gene Proteins 0.000 claims description 4
• 102100032937 CD40 ligand Human genes 0.000 claims description 4
• 108010065524 CD52 Antigen Proteins 0.000 claims description 4
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 4
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 4
• 190000008236 Carboplatin Chemical compound 0.000 claims description 4
• 108010012236 Chemokines Proteins 0.000 claims description 4
• 102000019034 Chemokines Human genes 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 4
• 208000014311 Cushing syndrome Diseases 0.000 claims description 4
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 4
• 108010092160 Dactinomycin Proteins 0.000 claims description 4
• 101100044298 Drosophila melanogaster fand gene Proteins 0.000 claims description 4
• 102100023688 Eotaxin Human genes 0.000 claims description 4
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 4
• 101150064015 FAS gene Proteins 0.000 claims description 4
• 108010039471 Fas Ligand Protein Proteins 0.000 claims description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
• 108010072051 Glatiramer Acetate Proteins 0.000 claims description 4
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 4
• 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 claims description 4
• 208000015023 Graves' disease Diseases 0.000 claims description 4
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 4
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 4
• 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 claims description 4
• 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 claims description 4
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 4
• 101000978392 Homo sapiens Eotaxin Proteins 0.000 claims description 4
• 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 claims description 4
• 101001033279 Homo sapiens Interleukin-3 Proteins 0.000 claims description 4
• 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 claims description 4
• 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 claims description 4
• 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 claims description 4
• 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 claims description 4
• 101000610602 Homo sapiens Tumor necrosis factor receptor superfamily member 10C Proteins 0.000 claims description 4
• 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 claims description 4
• 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 claims description 4
• 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 4
• 101000679921 Homo sapiens Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 claims description 4
• 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 claims description 4
• 101000679907 Homo sapiens Tumor necrosis factor receptor superfamily member 27 Proteins 0.000 claims description 4
• 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 claims description 4
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 4
• 102000026633 IL6 Human genes 0.000 claims description 4
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 4
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 4
• 108010005714 Interferon beta-1b Proteins 0.000 claims description 4
• 102100020881 Interleukin-1 alpha Human genes 0.000 claims description 4
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 claims description 4
• 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 claims description 4
• 108090000174 Interleukin-10 Proteins 0.000 claims description 4
• 102000003814 Interleukin-10 Human genes 0.000 claims description 4
• 108090000177 Interleukin-11 Proteins 0.000 claims description 4
• 102000003815 Interleukin-11 Human genes 0.000 claims description 4
• 102000013462 Interleukin-12 Human genes 0.000 claims description 4
• 108010065805 Interleukin-12 Proteins 0.000 claims description 4
• 102000003816 Interleukin-13 Human genes 0.000 claims description 4
• 108090000176 Interleukin-13 Proteins 0.000 claims description 4
• 108090000172 Interleukin-15 Proteins 0.000 claims description 4
• 102000003812 Interleukin-15 Human genes 0.000 claims description 4
• 102100039064 Interleukin-3 Human genes 0.000 claims description 4
• 102000004388 Interleukin-4 Human genes 0.000 claims description 4
• 108090000978 Interleukin-4 Proteins 0.000 claims description 4
• 102000000743 Interleukin-5 Human genes 0.000 claims description 4
• 108010002616 Interleukin-5 Proteins 0.000 claims description 4
• 108090001005 Interleukin-6 Proteins 0.000 claims description 4
• 102000000585 Interleukin-9 Human genes 0.000 claims description 4
• 108010002335 Interleukin-9 Proteins 0.000 claims description 4
• 102000015696 Interleukins Human genes 0.000 claims description 4
• 108010063738 Interleukins Proteins 0.000 claims description 4
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
• 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 4
• 101100207071 Mus musculus Tnfsf8 gene Proteins 0.000 claims description 4
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
• 229930012538 Paclitaxel Natural products 0.000 claims description 4
• 101100335198 Pneumocystis carinii fol1 gene Proteins 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 4
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 4
• 108010025832 RANK Ligand Proteins 0.000 claims description 4
• 206010039710 Scleroderma Diseases 0.000 claims description 4
• 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 claims description 4
• 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 claims description 4
• 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 claims description 4
• 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 claims description 4
• 108090000138 Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 claims description 4
• 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 claims description 4
• 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 claims description 4
• 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 claims description 4
• 102100040115 Tumor necrosis factor receptor superfamily member 10C Human genes 0.000 claims description 4
• 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 claims description 4
• 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 claims description 4
• 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims description 4
• 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 claims description 4
• 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 claims description 4
• 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 claims description 4
• 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 claims description 4
• 102100022202 Tumor necrosis factor receptor superfamily member 27 Human genes 0.000 claims description 4
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 4
• 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 claims description 4
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 4
• 206010047115 Vasculitis Diseases 0.000 claims description 4
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 4
• VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 claims description 4
• XYVNHPYNSPGYLI-UUOKFMHZSA-N [(2r,3s,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-4-hydroxy-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O XYVNHPYNSPGYLI-UUOKFMHZSA-N 0.000 claims description 4
• 229960003697 abatacept Drugs 0.000 claims description 4
• 229960000446 abciximab Drugs 0.000 claims description 4
• 229940119059 actemra Drugs 0.000 claims description 4
• 229930183665 actinomycin Natural products 0.000 claims description 4
• 229950005725 arcitumomab Drugs 0.000 claims description 4
• 229940057415 aubagio Drugs 0.000 claims description 4
• 229940120638 avastin Drugs 0.000 claims description 4
• 229940003504 avonex Drugs 0.000 claims description 4
• 229960002756 azacitidine Drugs 0.000 claims description 4
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 4
• 229960002170 azathioprine Drugs 0.000 claims description 4
• 229960004669 basiliximab Drugs 0.000 claims description 4
• 229940021459 betaseron Drugs 0.000 claims description 4
• 229960000397 bevacizumab Drugs 0.000 claims description 4
• 229960001561 bleomycin Drugs 0.000 claims description 4
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 4
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 4
• 229960001467 bortezomib Drugs 0.000 claims description 4
• 229940112129 campath Drugs 0.000 claims description 4
• 229960004117 capecitabine Drugs 0.000 claims description 4
• 229940034605 capromab pendetide Drugs 0.000 claims description 4
• 229960004562 carboplatin Drugs 0.000 claims description 4
• 229960005395 cetuximab Drugs 0.000 claims description 4
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 4
• 229960004630 chlorambucil Drugs 0.000 claims description 4
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims description 4
• 229940090100 cimzia Drugs 0.000 claims description 4
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
• 229960004316 cisplatin Drugs 0.000 claims description 4
• 229940038717 copaxone Drugs 0.000 claims description 4
• 229960004397 cyclophosphamide Drugs 0.000 claims description 4
• 229960000684 cytarabine Drugs 0.000 claims description 4
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 4
• 229960000975 daunorubicin Drugs 0.000 claims description 4
• 229960001251 denosumab Drugs 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims description 4
• 229960003668 docetaxel Drugs 0.000 claims description 4
• ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 claims description 4
• 229950005454 doxifluridine Drugs 0.000 claims description 4
• 229960004679 doxorubicin Drugs 0.000 claims description 4
• 229960001776 edrecolomab Drugs 0.000 claims description 4
• 229960000284 efalizumab Drugs 0.000 claims description 4
• 150000002066 eicosanoids Chemical class 0.000 claims description 4
• 229940073621 enbrel Drugs 0.000 claims description 4
• 229960001904 epirubicin Drugs 0.000 claims description 4
• 229930013356 epothilone Natural products 0.000 claims description 4
• 150000003883 epothilone derivatives Chemical class 0.000 claims description 4
• 229940082789 erbitux Drugs 0.000 claims description 4
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 4
• 229960005420 etoposide Drugs 0.000 claims description 4
• 229960002949 fluorouracil Drugs 0.000 claims description 4
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 4
• 229960005277 gemcitabine Drugs 0.000 claims description 4
• 229960000578 gemtuzumab Drugs 0.000 claims description 4
• 229960003297 gemtuzumab ozogamicin Drugs 0.000 claims description 4
• 229960001743 golimumab Drugs 0.000 claims description 4
• 229940022353 herceptin Drugs 0.000 claims description 4
• 229960000908 idarubicin Drugs 0.000 claims description 4
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 4
• 229960002411 imatinib Drugs 0.000 claims description 4
• 229940047124 interferons Drugs 0.000 claims description 4
• 229940047122 interleukins Drugs 0.000 claims description 4
• 229960004768 irinotecan Drugs 0.000 claims description 4
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 4
• 229940054136 kineret Drugs 0.000 claims description 4
• 229940047834 lemtrada Drugs 0.000 claims description 4
• 206010025135 lupus erythematosus Diseases 0.000 claims description 4
• 229950008001 matuzumab Drugs 0.000 claims description 4
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 4
• 229960004961 mechlorethamine Drugs 0.000 claims description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
• 229960001428 mercaptopurine Drugs 0.000 claims description 4
• 229960000485 methotrexate Drugs 0.000 claims description 4
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 4
• 229960001156 mitoxantrone Drugs 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 229950010203 nimotuzumab Drugs 0.000 claims description 4
• 229960000470 omalizumab Drugs 0.000 claims description 4
• 229940035567 orencia Drugs 0.000 claims description 4
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 4
• 229960001756 oxaliplatin Drugs 0.000 claims description 4
• 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 4
• 229960001592 paclitaxel Drugs 0.000 claims description 4
• 229960000402 palivizumab Drugs 0.000 claims description 4
• 108010027737 peginterferon beta-1a Proteins 0.000 claims description 4
• 229960005079 pemetrexed Drugs 0.000 claims description 4
• QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 229940007060 plegridy Drugs 0.000 claims description 4
• 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 4
• 150000003180 prostaglandins Chemical class 0.000 claims description 4
• 229940038850 rebif Drugs 0.000 claims description 4
• 229940107685 reopro Drugs 0.000 claims description 4
• 201000000306 sarcoidosis Diseases 0.000 claims description 4
• 229940068638 simponi Drugs 0.000 claims description 4
• 229940115586 simulect Drugs 0.000 claims description 4
• 210000000952 spleen Anatomy 0.000 claims description 4
• 229950010708 sulesomab Drugs 0.000 claims description 4
• 229940036185 synagis Drugs 0.000 claims description 4
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 4
• 229940121136 tecfidera Drugs 0.000 claims description 4
• 229950008860 technetium (99mtc) fanolesomab Drugs 0.000 claims description 4
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 4
• 229960001278 teniposide Drugs 0.000 claims description 4
• 229960000331 teriflunomide Drugs 0.000 claims description 4
• 210000001541 thymus gland Anatomy 0.000 claims description 4
• 229960003087 tioguanine Drugs 0.000 claims description 4
• MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 4
• 229960000303 topotecan Drugs 0.000 claims description 4
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 4
• 229960000575 trastuzumab Drugs 0.000 claims description 4
• 229960000653 valrubicin Drugs 0.000 claims description 4
• ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 claims description 4
• 229960003048 vinblastine Drugs 0.000 claims description 4
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 4
• 229960004528 vincristine Drugs 0.000 claims description 4
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 4
• 229960004355 vindesine Drugs 0.000 claims description 4
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims description 4
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 4
• 229960002066 vinorelbine Drugs 0.000 claims description 4
• 229940099073 xolair Drugs 0.000 claims description 4
• 101000610609 Homo sapiens Tumor necrosis factor receptor superfamily member 10D Proteins 0.000 claims description 3
• 108091058560 IL8 Proteins 0.000 claims description 3
• 102000004890 Interleukin-8 Human genes 0.000 claims description 3
• 108090001007 Interleukin-8 Proteins 0.000 claims description 3
• 206010052779 Transplant rejections Diseases 0.000 claims description 3
• 102100040110 Tumor necrosis factor receptor superfamily member 10D Human genes 0.000 claims description 3
• 210000001015 abdomen Anatomy 0.000 claims description 3
• 230000001919 adrenal effect Effects 0.000 claims description 3
• 210000000988 bone and bone Anatomy 0.000 claims description 3
• 210000000481 breast Anatomy 0.000 claims description 3
• 210000001072 colon Anatomy 0.000 claims description 3
• 210000002249 digestive system Anatomy 0.000 claims description 3
• 210000003372 endocrine gland Anatomy 0.000 claims description 3
• 239000012634 fragment Substances 0.000 claims description 3
• 210000004324 lymphatic system Anatomy 0.000 claims description 3
• 210000001672 ovary Anatomy 0.000 claims description 3
• 210000000496 pancreas Anatomy 0.000 claims description 3
• 230000000849 parathyroid Effects 0.000 claims description 3
• 230000002093 peripheral effect Effects 0.000 claims description 3
• 210000004303 peritoneum Anatomy 0.000 claims description 3
• 230000001817 pituitary effect Effects 0.000 claims description 3
• 210000002307 prostate Anatomy 0.000 claims description 3
• 210000001550 testis Anatomy 0.000 claims description 3
• 210000000115 thoracic cavity Anatomy 0.000 claims description 3
• 210000001685 thyroid gland Anatomy 0.000 claims description 3
• 101000920026 Homo sapiens Tumor necrosis factor receptor superfamily member EDAR Proteins 0.000 claims description 2
• 102100030810 Tumor necrosis factor receptor superfamily member EDAR Human genes 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 4
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 1
• 102100026882 Alpha-synuclein Human genes 0.000 claims 1
• 102100025221 CD70 antigen Human genes 0.000 claims 1
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 1
• 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 claims 1
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims 1
• 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims 1
• 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 claims 1
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims 1
• 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 claims 1
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 claims 1
• 102100026720 Interferon beta Human genes 0.000 claims 1
• 108010047761 Interferon-alpha Proteins 0.000 claims 1
• 102000006992 Interferon-alpha Human genes 0.000 claims 1
• 108090000467 Interferon-beta Proteins 0.000 claims 1
• 102000000704 Interleukin-7 Human genes 0.000 claims 1
• 101100046559 Mus musculus Tnfrsf12a gene Proteins 0.000 claims 1
• 102000015336 Nerve Growth Factor Human genes 0.000 claims 1
• 108010025020 Nerve Growth Factor Proteins 0.000 claims 1
• 102000014128 RANK Ligand Human genes 0.000 claims 1
• 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 claims 1
• 101150056647 TNFRSF4 gene Proteins 0.000 claims 1
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 claims 1
• 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 claims 1
• 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 claims 1
• 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 claims 1
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 claims 1
• 229960000403 etanercept Drugs 0.000 claims 1
• OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims 1
• 101710144268 B- and T-lymphocyte attenuator Proteins 0.000 description 193
• 210000004027 cell Anatomy 0.000 description 117
• 235000018102 proteins Nutrition 0.000 description 95
• 230000027455 binding Effects 0.000 description 76
• 230000011664 signaling Effects 0.000 description 52
• 239000003446 ligand Substances 0.000 description 50
• 102220571043 Protein CFAP210_L70E_mutation Human genes 0.000 description 44
• 102220506859 Small proline-rich protein 3_L70N_mutation Human genes 0.000 description 44
• 230000004913 activation Effects 0.000 description 31
• 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 29
• 102100024263 CD160 antigen Human genes 0.000 description 28
• 241000701022 Cytomegalovirus Species 0.000 description 25
• 239000004005 microsphere Substances 0.000 description 25
• 210000001744 T-lymphocyte Anatomy 0.000 description 24
• 206010025323 Lymphomas Diseases 0.000 description 22
• 239000000556 agonist Substances 0.000 description 22
• 238000000034 method Methods 0.000 description 22
• 230000014509 gene expression Effects 0.000 description 21
• 210000003719 b-lymphocyte Anatomy 0.000 description 20
• 230000002401 inhibitory effect Effects 0.000 description 19
• 238000010186 staining Methods 0.000 description 17
• 230000037361 pathway Effects 0.000 description 16
• 201000010099 disease Diseases 0.000 description 13
• 230000003993 interaction Effects 0.000 description 13
• 102000005962 receptors Human genes 0.000 description 13
• 108020003175 receptors Proteins 0.000 description 13
• 230000003612 virological effect Effects 0.000 description 13
• 108091006020 Fc-tagged proteins Proteins 0.000 description 12
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
• 210000000822 natural killer cell Anatomy 0.000 description 11
• 208000017604 Hodgkin disease Diseases 0.000 description 10
• 239000000427 antigen Substances 0.000 description 10
• 102000036639 antigens Human genes 0.000 description 10
• 108091007433 antigens Proteins 0.000 description 10
• 230000001965 increasing effect Effects 0.000 description 10
• 208000003174 Brain Neoplasms Diseases 0.000 description 9
• 108060003951 Immunoglobulin Proteins 0.000 description 9
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 9
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 9
• 210000000987 immune system Anatomy 0.000 description 9
• 102000018358 immunoglobulin Human genes 0.000 description 9
• 244000052769 pathogen Species 0.000 description 9
• 102000007469 Actins Human genes 0.000 description 8
• 108010085238 Actins Proteins 0.000 description 8
• 206010039491 Sarcoma Diseases 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
• 230000035935 pregnancy Effects 0.000 description 8
• 238000001262 western blot Methods 0.000 description 8
• 230000001154 acute effect Effects 0.000 description 7
• 108091008042 inhibitory receptors Proteins 0.000 description 7
• 208000032839 leukemia Diseases 0.000 description 7
• DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• 201000004624 Dermatitis Diseases 0.000 description 6
• 206010018338 Glioma Diseases 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 6
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 6
• 241000700605 Viruses Species 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 230000005754 cellular signaling Effects 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 230000002496 gastric effect Effects 0.000 description 6
• 230000002757 inflammatory effect Effects 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 230000001105 regulatory effect Effects 0.000 description 6
• 206010006187 Breast cancer Diseases 0.000 description 5
• 208000026310 Breast neoplasm Diseases 0.000 description 5
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 5
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 5
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 5
• 102100021592 Interleukin-7 Human genes 0.000 description 5
• 241000699666 Mus <mouse, genus> Species 0.000 description 5
• 101100058686 Mus musculus Btla gene Proteins 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
• 239000004698 Polyethylene Substances 0.000 description 5
• 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 description 5
• 230000003213 activating effect Effects 0.000 description 5
• 230000001270 agonistic effect Effects 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 201000003444 follicular lymphoma Diseases 0.000 description 5
• 230000004927 fusion Effects 0.000 description 5
• 102000053464 human BTLA Human genes 0.000 description 5
• 208000026278 immune system disease Diseases 0.000 description 5
• 229940072221 immunoglobulins Drugs 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000003278 mimic effect Effects 0.000 description 5
• 239000000203 mixture Substances 0.000 description 5
• 238000002703 mutagenesis Methods 0.000 description 5
• 231100000350 mutagenesis Toxicity 0.000 description 5
• 230000001717 pathogenic effect Effects 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 206010003571 Astrocytoma Diseases 0.000 description 4
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 4
• 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
• 102100025137 Early activation antigen CD69 Human genes 0.000 description 4
• 208000021309 Germ cell tumor Diseases 0.000 description 4
• 208000032612 Glial tumor Diseases 0.000 description 4
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 4
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
• 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 4
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
• 102000008300 Mutant Proteins Human genes 0.000 description 4
• 108010021466 Mutant Proteins Proteins 0.000 description 4
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 4
• 206010034277 Pemphigoid Diseases 0.000 description 4
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
• 108091008874 T cell receptors Proteins 0.000 description 4
• 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 4
• 101710128901 Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 description 4
• 235000001014 amino acid Nutrition 0.000 description 4
• 229940024606 amino acid Drugs 0.000 description 4
• 230000008901 benefit 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
• 230000002267 hypothalamic effect Effects 0.000 description 4
• DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 208000027866 inflammatory disease Diseases 0.000 description 4
• 201000007270 liver cancer Diseases 0.000 description 4
• 230000019491 signal transduction Effects 0.000 description 4
• 201000000849 skin cancer Diseases 0.000 description 4
• 230000000638 stimulation Effects 0.000 description 4
• 210000002784 stomach Anatomy 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 102000007499 CD27 Ligand Human genes 0.000 description 3
• 201000009030 Carcinoma Diseases 0.000 description 3
• 102000000844 Cell Surface Receptors Human genes 0.000 description 3
• 108010001857 Cell Surface Receptors Proteins 0.000 description 3
• 102000015212 Fas Ligand Protein Human genes 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 3
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 3
• 108010014726 Interferon Type I Proteins 0.000 description 3
• 102000002227 Interferon Type I Human genes 0.000 description 3
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 3
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
• 101710116676 Membrane glycoprotein UL144 Proteins 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 101100425741 Mus musculus Tnfrsf14 gene Proteins 0.000 description 3
• 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
• 229930040373 Paraformaldehyde Natural products 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• 208000000453 Skin Neoplasms Diseases 0.000 description 3
• 230000006052 T cell proliferation Effects 0.000 description 3
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
• 108010000449 TNF-Related Apoptosis-Inducing Ligand Receptors Proteins 0.000 description 3
• 102000002259 TNF-Related Apoptosis-Inducing Ligand Receptors Human genes 0.000 description 3
• 108091008003 TRAIL-RI Proteins 0.000 description 3
• 102100024568 Tumor necrosis factor ligand superfamily member 11 Human genes 0.000 description 3
• 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 3
• 230000008484 agonism Effects 0.000 description 3
• 239000012491 analyte Substances 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 229940088710 antibiotic agent Drugs 0.000 description 3
• 230000005784 autoimmunity Effects 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 208000002458 carcinoid tumor Diseases 0.000 description 3
• 230000001461 cytolytic effect Effects 0.000 description 3
• 210000004443 dendritic cell Anatomy 0.000 description 3
• 230000002708 enhancing effect Effects 0.000 description 3
• 210000002443 helper t lymphocyte Anatomy 0.000 description 3
• 229960002751 imiquimod Drugs 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 229940079322 interferon Drugs 0.000 description 3
• 238000010212 intracellular staining Methods 0.000 description 3
• 210000004153 islets of langerhan Anatomy 0.000 description 3
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 3
• 208000003747 lymphoid leukemia Diseases 0.000 description 3
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 201000001441 melanoma Diseases 0.000 description 3
• 201000005962 mycosis fungoides Diseases 0.000 description 3
• 201000002528 pancreatic cancer Diseases 0.000 description 3
• 208000008443 pancreatic carcinoma Diseases 0.000 description 3
• 229920002866 paraformaldehyde Polymers 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 229920001184 polypeptide Polymers 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 230000000770 proinflammatory effect Effects 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 230000000392 somatic effect Effects 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 201000008205 supratentorial primitive neuroectodermal tumor Diseases 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• 210000000239 visual pathway Anatomy 0.000 description 3
• 230000004400 visual pathway Effects 0.000 description 3
• 208000030507 AIDS Diseases 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• 108010083359 Antigen Receptors Proteins 0.000 description 2
• 102000006306 Antigen Receptors Human genes 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 206010060971 Astrocytoma malignant Diseases 0.000 description 2
• 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 2
• 108091008875 B cell receptors Proteins 0.000 description 2
• 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 description 2
• 206010004593 Bile duct cancer Diseases 0.000 description 2
• 206010005003 Bladder cancer Diseases 0.000 description 2
• 206010006143 Brain stem glioma Diseases 0.000 description 2
• 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 2
• 206010007275 Carcinoid tumour Diseases 0.000 description 2
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 2
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 2
• 206010009944 Colon cancer Diseases 0.000 description 2
• 206010014967 Ependymoma Diseases 0.000 description 2
• 208000019028 Epidermal thickening Diseases 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 208000012468 Ewing sarcoma/peripheral primitive neuroectodermal tumor Diseases 0.000 description 2
• 208000007465 Giant cell arteritis Diseases 0.000 description 2
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
• 208000010159 IgA glomerulonephritis Diseases 0.000 description 2
• 206010021263 IgA nephropathy Diseases 0.000 description 2
• 206010061252 Intraocular melanoma Diseases 0.000 description 2
• 208000003456 Juvenile Arthritis Diseases 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• 101150073396 LTA gene Proteins 0.000 description 2
• 206010023825 Laryngeal cancer Diseases 0.000 description 2
• 208000032514 Leukocytoclastic vasculitis Diseases 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• 206010025557 Malignant fibrous histiocytoma of bone Diseases 0.000 description 2
• 208000000172 Medulloblastoma Diseases 0.000 description 2
• 208000012192 Mucous membrane pemphigoid Diseases 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 description 2
• 101100102346 Mus musculus Vangl2 gene Proteins 0.000 description 2
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 2
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 2
• 208000008223 Pemphigoid Gestationis Diseases 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 2
• 206010048895 Pityriasis lichenoides et varioliformis acuta Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000012083 RIPA buffer Substances 0.000 description 2
• 201000000582 Retinoblastoma Diseases 0.000 description 2
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
• 108010029477 STAT5 Transcription Factor Proteins 0.000 description 2
• 102100024481 Signal transducer and activator of transcription 5A Human genes 0.000 description 2
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 2
• 208000006045 Spondylarthropathies Diseases 0.000 description 2
• 206010042276 Subacute endocarditis Diseases 0.000 description 2
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
• 201000009365 Thymic carcinoma Diseases 0.000 description 2
• 208000024770 Thyroid neoplasm Diseases 0.000 description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
• 201000005969 Uveal melanoma Diseases 0.000 description 2
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 208000020990 adrenal cortex carcinoma Diseases 0.000 description 2
• 208000007128 adrenocortical carcinoma Diseases 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000003042 antagnostic effect Effects 0.000 description 2
• 230000030741 antigen processing and presentation Effects 0.000 description 2
• 230000000890 antigenic effect Effects 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 201000007335 cerebellar astrocytoma Diseases 0.000 description 2
• 208000030239 cerebral astrocytoma Diseases 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• HJWLJNBZVZDLAQ-HAQNSBGRSA-N chembl2103874 Chemical compound C1C[C@@H](CS(=O)(=O)NC)CC[C@@H]1N(C)C1=NC=NC2=C1C=CN2 HJWLJNBZVZDLAQ-HAQNSBGRSA-N 0.000 description 2
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 2
• 201000010002 cicatricial pemphigoid Diseases 0.000 description 2
• 230000004186 co-expression Effects 0.000 description 2
• 238000002742 combinatorial mutagenesis Methods 0.000 description 2
• 230000002596 correlated effect Effects 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 208000037765 diseases and disorders Diseases 0.000 description 2
• 239000012636 effector Substances 0.000 description 2
• 206010014599 encephalitis Diseases 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• 208000024519 eye neoplasm Diseases 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 210000003128 head Anatomy 0.000 description 2
• 208000029824 high grade glioma Diseases 0.000 description 2
• 210000004408 hybridoma Anatomy 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
• 210000000244 kidney pelvis Anatomy 0.000 description 2
• 206010023841 laryngeal neoplasm Diseases 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 208000030883 malignant astrocytoma Diseases 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 201000011614 malignant glioma Diseases 0.000 description 2
• 208000006178 malignant mesothelioma Diseases 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 210000004379 membrane Anatomy 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 208000025113 myeloid leukemia Diseases 0.000 description 2
• 208000018795 nasal cavity and paranasal sinus carcinoma Diseases 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 201000008106 ocular cancer Diseases 0.000 description 2
• 201000002575 ocular melanoma Diseases 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 2
• AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
• 208000010626 plasma cell neoplasm Diseases 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 229940044601 receptor agonist Drugs 0.000 description 2
• 239000000018 receptor agonist Substances 0.000 description 2
• 230000007115 recruitment Effects 0.000 description 2
• GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 102000034285 signal transducing proteins Human genes 0.000 description 2
• 108091006024 signal transducing proteins Proteins 0.000 description 2
• 238000002741 site-directed mutagenesis Methods 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 201000005671 spondyloarthropathy Diseases 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 208000008467 subacute bacterial endocarditis Diseases 0.000 description 2
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 201000002510 thyroid cancer Diseases 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 206010044412 transitional cell carcinoma Diseases 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
• 208000018417 undifferentiated high grade pleomorphic sarcoma of bone Diseases 0.000 description 2
• 210000000626 ureter Anatomy 0.000 description 2
• 201000005112 urinary bladder cancer Diseases 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N &alpha;-D-glucopyranosyl-&alpha;-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
• QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
• 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
• 206010056508 Acquired epidermolysis bullosa Diseases 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 206010000748 Acute febrile neutrophilic dermatosis Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000002485 Adiposis dolorosa Diseases 0.000 description 1
• 208000008190 Agammaglobulinemia Diseases 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
• 206010001935 American trypanosomiasis Diseases 0.000 description 1
• 206010061424 Anal cancer Diseases 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
• 208000001839 Antisynthetase syndrome Diseases 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 206010003645 Atopy Diseases 0.000 description 1
• 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
• 206010071576 Autoimmune aplastic anaemia Diseases 0.000 description 1
• 208000000659 Autoimmune lymphoproliferative syndrome Diseases 0.000 description 1
• 206010069002 Autoimmune pancreatitis Diseases 0.000 description 1
• 208000022106 Autoimmune polyendocrinopathy type 2 Diseases 0.000 description 1
• 102000019260 B-Cell Antigen Receptors Human genes 0.000 description 1
• 108010012919 B-Cell Antigen Receptors Proteins 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 201000002827 Balo concentric sclerosis Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
• 208000009766 Blau syndrome Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 201000006390 Brachial Plexus Neuritis Diseases 0.000 description 1
• 102100023705 C-C motif chemokine 14 Human genes 0.000 description 1
• 102100036842 C-C motif chemokine 19 Human genes 0.000 description 1
• 102100036848 C-C motif chemokine 20 Human genes 0.000 description 1
• 102100036846 C-C motif chemokine 21 Human genes 0.000 description 1
• 102100021933 C-C motif chemokine 25 Human genes 0.000 description 1
• 102100021936 C-C motif chemokine 27 Human genes 0.000 description 1
• 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 1
• 201000002829 CREST Syndrome Diseases 0.000 description 1
• 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
• 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
• 229940045513 CTLA4 antagonist Drugs 0.000 description 1
• 206010007279 Carcinoid tumour of the gastrointestinal tract Diseases 0.000 description 1
• 208000005024 Castleman disease Diseases 0.000 description 1
• 206010063094 Cerebral malaria Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 208000024699 Chagas disease Diseases 0.000 description 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
• 206010008748 Chorea Diseases 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 201000000724 Chronic recurrent multifocal osteomyelitis Diseases 0.000 description 1
• 208000006344 Churg-Strauss Syndrome Diseases 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
• 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 1
• 206010073140 Clear cell sarcoma of soft tissue Diseases 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 208000010007 Cogan syndrome Diseases 0.000 description 1
• 208000011038 Cold agglutinin disease Diseases 0.000 description 1
• 206010009868 Cold type haemolytic anaemia Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 206010010252 Concentric sclerosis Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 208000019707 Cryoglobulinemic vasculitis Diseases 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 206010011953 Decreased activity Diseases 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• 206010012468 Dermatitis herpetiformis Diseases 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
• 201000003066 Diffuse Scleroderma Diseases 0.000 description 1
• 208000024134 Diffuse cutaneous systemic sclerosis Diseases 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 201000009273 Endometriosis Diseases 0.000 description 1
• 101710091045 Envelope protein Proteins 0.000 description 1
• 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
• 241000283074 Equus asinus Species 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 206010015226 Erythema nodosum Diseases 0.000 description 1
• 206010015251 Erythroblastosis foetalis Diseases 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 208000004332 Evans syndrome Diseases 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 208000017259 Extragonadal germ cell tumor Diseases 0.000 description 1
• 206010016228 Fasciitis Diseases 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 206010068715 Fibrodysplasia ossificans progressiva Diseases 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 206010018364 Glomerulonephritis 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
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 208000016905 Hashimoto encephalopathy Diseases 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 201000004331 Henoch-Schoenlein purpura Diseases 0.000 description 1
• 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
• 206010019939 Herpes gestationis Diseases 0.000 description 1
• 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
• 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
• 101000978381 Homo sapiens C-C motif chemokine 14 Proteins 0.000 description 1
• 101000713106 Homo sapiens C-C motif chemokine 19 Proteins 0.000 description 1
• 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 1
• 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 description 1
• 101000897486 Homo sapiens C-C motif chemokine 25 Proteins 0.000 description 1
• 101000897494 Homo sapiens C-C motif chemokine 27 Proteins 0.000 description 1
• 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 1
• 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
• 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 1
• 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 description 1
• 101000617285 Homo sapiens Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 description 1
• 208000029470 Hughes-Stovin syndrome Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
• 206010021042 Hypopharyngeal cancer Diseases 0.000 description 1
• 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
• 208000031814 IgA Vasculitis Diseases 0.000 description 1
• 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
• 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
• 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 1
• 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 1
• 208000005615 Interstitial Cystitis Diseases 0.000 description 1
• 208000000209 Isaacs syndrome Diseases 0.000 description 1
• 102000042838 JAK family Human genes 0.000 description 1
• 102000015617 Janus Kinases Human genes 0.000 description 1
• 108010024121 Janus Kinases Proteins 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000011200 Kawasaki disease Diseases 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
• 208000032420 Latent Infection Diseases 0.000 description 1
• 208000034624 Leukocytoclastic Cutaneous Vasculitis Diseases 0.000 description 1
• 206010024434 Lichen sclerosus Diseases 0.000 description 1
• 208000012309 Linear IgA disease Diseases 0.000 description 1
• 206010062038 Lip neoplasm Diseases 0.000 description 1
• 208000000185 Localized scleroderma Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 206010062049 Lymphocytic infiltration Diseases 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• 102000008072 Lymphokines Human genes 0.000 description 1
• 108010074338 Lymphokines Proteins 0.000 description 1
• 206010025312 Lymphoma AIDS related Diseases 0.000 description 1
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 208000009777 Majeed syndrome Diseases 0.000 description 1
• 208000004059 Male Breast Neoplasms Diseases 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 206010064281 Malignant atrophic papulosis Diseases 0.000 description 1
• 208000030070 Malignant epithelial tumor of ovary Diseases 0.000 description 1
• 206010073059 Malignant neoplasm of unknown primary site Diseases 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 208000027530 Meniere disease Diseases 0.000 description 1
• 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
• 206010027982 Morphoea Diseases 0.000 description 1
• 208000003445 Mouth Neoplasms Diseases 0.000 description 1
• 206010028424 Myasthenic syndrome Diseases 0.000 description 1
• 102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
• OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
• MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 108010057466 NF-kappa B Proteins 0.000 description 1
• 102000003945 NF-kappa B Human genes 0.000 description 1
• 230000006051 NK cell activation Effects 0.000 description 1
• 206010029229 Neuralgic amyotrophy Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
• 206010072359 Neuromyotonia Diseases 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 240000008881 Oenanthe javanica Species 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 208000005225 Opsoclonus-Myoclonus Syndrome Diseases 0.000 description 1
• 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
• 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
• 108010058846 Ovalbumin Proteins 0.000 description 1
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
• 206010033268 Ovarian low malignant potential tumour Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010053869 POEMS syndrome Diseases 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 206010048705 Paraneoplastic cerebellar degeneration Diseases 0.000 description 1
• 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
• 208000004788 Pars Planitis Diseases 0.000 description 1
• 201000011152 Pemphigus Diseases 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 208000031845 Pernicious anaemia Diseases 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 208000000766 Pityriasis Lichenoides Diseases 0.000 description 1
• 102220518747 Plasma serine protease inhibitor_N61A_mutation Human genes 0.000 description 1
• 241000224021 Plasmodium berghei ANKA Species 0.000 description 1
• 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
• 206010065159 Polychondritis Diseases 0.000 description 1
• 208000007048 Polymyalgia Rheumatica Diseases 0.000 description 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
• 208000037534 Progressive hemifacial atrophy Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 101710188315 Protein X Proteins 0.000 description 1
• 208000003670 Pure Red-Cell Aplasia Diseases 0.000 description 1
• 238000002123 RNA extraction Methods 0.000 description 1
• 208000003782 Raynaud disease Diseases 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 208000005793 Restless legs syndrome Diseases 0.000 description 1
• 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 1
• 108010061033 SH2 Domain-Containing Protein Tyrosine Phosphatases Proteins 0.000 description 1
• 102000011859 SH2 Domain-Containing Protein Tyrosine Phosphatases Human genes 0.000 description 1
• 108010044012 STAT1 Transcription Factor Proteins 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• 201000010848 Schnitzler Syndrome Diseases 0.000 description 1
• 206010039705 Scleritis Diseases 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 208000032384 Severe immune-mediated enteropathy Diseases 0.000 description 1
• 208000009359 Sezary Syndrome Diseases 0.000 description 1
• 208000021388 Sezary disease Diseases 0.000 description 1
• 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 206010072148 Stiff-Person syndrome Diseases 0.000 description 1
• 241000194017 Streptococcus Species 0.000 description 1
• 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
• 102220577258 Stromal cell-derived factor 1_R62A_mutation Human genes 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 208000002286 Susac Syndrome Diseases 0.000 description 1
• 208000010265 Sweet syndrome Diseases 0.000 description 1
• 208000027522 Sydenham chorea Diseases 0.000 description 1
• 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 230000020385 T cell costimulation Effects 0.000 description 1
• 230000024932 T cell mediated immunity Effects 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000001106 Takayasu Arteritis Diseases 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 210000004241 Th2 cell Anatomy 0.000 description 1
• 102000002689 Toll-like receptor Human genes 0.000 description 1
• 108020000411 Toll-like receptor Proteins 0.000 description 1
• 206010051526 Tolosa-Hunt syndrome Diseases 0.000 description 1
• 102000000887 Transcription factor STAT Human genes 0.000 description 1
• 108050007918 Transcription factor STAT Proteins 0.000 description 1
• 206010044407 Transitional cell cancer of the renal pelvis and ureter Diseases 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• 241000223109 Trypanosoma cruzi Species 0.000 description 1
• 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 1
• 102100024586 Tumor necrosis factor ligand superfamily member 14 Human genes 0.000 description 1
• 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 description 1
• 206010054094 Tumour necrosis Diseases 0.000 description 1
• 102220524251 Ubiquitin-related modifier 1_T49G_mutation Human genes 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 206010046431 Urethral cancer Diseases 0.000 description 1
• 206010046458 Urethral neoplasms Diseases 0.000 description 1
• 102220488256 Uromodulin-like 1_R42D_mutation Human genes 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 206010047642 Vitiligo Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 1
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 210000005006 adaptive immune system Anatomy 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 230000001780 adrenocortical effect Effects 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 238000012867 alanine scanning Methods 0.000 description 1
• 229940060265 aldara Drugs 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 208000004631 alopecia areata Diseases 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 238000011230 antibody-based therapy Methods 0.000 description 1
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 201000011165 anus cancer Diseases 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 201000004984 autoimmune cardiomyopathy Diseases 0.000 description 1
• 208000001974 autoimmune enteropathy Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 208000027625 autoimmune inner ear disease Diseases 0.000 description 1
• 201000004339 autoimmune neuropathy Diseases 0.000 description 1
• 201000005011 autoimmune peripheral neuropathy Diseases 0.000 description 1
• 201000011385 autoimmune polyendocrine syndrome Diseases 0.000 description 1
• 201000009780 autoimmune polyendocrine syndrome type 2 Diseases 0.000 description 1
• 206010071572 autoimmune progesterone dermatitis Diseases 0.000 description 1
• 208000029407 autoimmune urticaria Diseases 0.000 description 1
• 201000004982 autoimmune uveitis Diseases 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 229960001950 benzethonium chloride Drugs 0.000 description 1
• UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• 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
• 230000002457 bidirectional effect Effects 0.000 description 1
• 208000026900 bile duct neoplasm Diseases 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
• HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 201000008873 bone osteosarcoma Diseases 0.000 description 1
• 208000012172 borderline epithelial tumor of ovary Diseases 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 208000000594 bullous pemphigoid Diseases 0.000 description 1
• LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 102220345064 c.113T>A Human genes 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004640 cellular pathway Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 208000019069 chronic childhood arthritis Diseases 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000024376 chronic urticaria Diseases 0.000 description 1
• 201000000292 clear cell sarcoma Diseases 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000012761 co-transfection Methods 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 150000001875 compounds Chemical class 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 230000000139 costimulatory effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 201000003278 cryoglobulinemia Diseases 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 208000018261 cutaneous leukocytoclastic angiitis Diseases 0.000 description 1
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
• 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 230000010250 cytokine signaling pathway Effects 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
• 238000013480 data collection Methods 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000030609 dephosphorylation Effects 0.000 description 1
• 238000006209 dephosphorylation reaction Methods 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
• 229960002986 dinoprostone Drugs 0.000 description 1
• 150000002016 disaccharides Chemical class 0.000 description 1
• 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 201000004997 drug-induced lupus erythematosus Diseases 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 238000001378 electrochemiluminescence detection Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
• 201000009580 eosinophilic pneumonia Diseases 0.000 description 1
• 201000011114 epidermolysis bullosa acquisita Diseases 0.000 description 1
• 201000008819 extrahepatic bile duct carcinoma Diseases 0.000 description 1
• 208000002980 facial hemiatrophy Diseases 0.000 description 1
• 208000001031 fetal erythroblastosis Diseases 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000012224 gene deletion Methods 0.000 description 1
• 238000012239 gene modification Methods 0.000 description 1
• 230000004077 genetic alteration Effects 0.000 description 1
• 231100000118 genetic alteration Toxicity 0.000 description 1
• 230000005017 genetic modification Effects 0.000 description 1
• 235000013617 genetically modified food Nutrition 0.000 description 1
• 201000007116 gestational trophoblastic neoplasm Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 208000035474 group of disease Diseases 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 208000002557 hidradenitis Diseases 0.000 description 1
• 201000007162 hidradenitis suppurativa Diseases 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 230000005745 host immune response Effects 0.000 description 1
• 230000004727 humoral immunity Effects 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 201000006362 hypersensitivity vasculitis Diseases 0.000 description 1
• 201000006866 hypopharynx cancer Diseases 0.000 description 1
• 102000027596 immune receptors Human genes 0.000 description 1
• 108091008915 immune receptors Proteins 0.000 description 1
• 230000008073 immune recognition Effects 0.000 description 1
• 230000037451 immune surveillance Effects 0.000 description 1
• 230000006058 immune tolerance Effects 0.000 description 1
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 201000008319 inclusion body myositis Diseases 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 238000012933 kinetic analysis Methods 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 201000011486 lichen planus Diseases 0.000 description 1
• 201000006721 lip cancer Diseases 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000012160 loading buffer Substances 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 210000000207 lymphocyte subset Anatomy 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 201000000564 macroglobulinemia Diseases 0.000 description 1
• 201000003175 male breast cancer Diseases 0.000 description 1
• 208000010907 male breast carcinoma Diseases 0.000 description 1
• 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000013507 mapping Methods 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 210000000716 merkel cell Anatomy 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Chemical class 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 208000037970 metastatic squamous neck cancer Diseases 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 238000002493 microarray Methods 0.000 description 1
• 206010063344 microscopic polyangiitis Diseases 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
• 206010051747 multiple endocrine neoplasia Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 208000008795 neuromyelitis optica Diseases 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 239000002736 nonionic surfactant Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 208000022982 optic pathway glioma Diseases 0.000 description 1
• 201000005443 oral cavity cancer Diseases 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 201000006958 oropharynx cancer Diseases 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
• 229940092253 ovalbumin Drugs 0.000 description 1
• 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• 201000005580 palindromic rheumatism Diseases 0.000 description 1
• 201000002530 pancreatic endocrine carcinoma Diseases 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 201000001976 pemphigus vulgaris Diseases 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 230000003094 perturbing effect Effects 0.000 description 1
• 208000028591 pheochromocytoma Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 201000003113 pineoblastoma Diseases 0.000 description 1
• 208000010916 pituitary tumor Diseases 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
• 230000004647 pro-inflammatory pathway Effects 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000008741 proinflammatory signaling process Effects 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
• KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 230000004850 protein–protein interaction Effects 0.000 description 1
• 201000009732 pulmonary eosinophilia Diseases 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 208000009954 pyoderma gangrenosum Diseases 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 208000009169 relapsing polychondritis Diseases 0.000 description 1
• 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
• 208000030859 renal pelvis/ureter urothelial carcinoma Diseases 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• 201000003068 rheumatic fever Diseases 0.000 description 1
• 102200060543 rs1060505037 Human genes 0.000 description 1
• 102200156919 rs116097205 Human genes 0.000 description 1
• 102220008839 rs193922287 Human genes 0.000 description 1
• 102220146261 rs199554805 Human genes 0.000 description 1
• 102200067541 rs281864846 Human genes 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 208000010157 sclerosing cholangitis Diseases 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• 206010040400 serum sickness Diseases 0.000 description 1
• 125000005629 sialic acid group Chemical group 0.000 description 1
• 230000020837 signal transduction in absence of ligand Effects 0.000 description 1
• 201000008261 skin carcinoma Diseases 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 201000002314 small intestine cancer Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 208000037969 squamous neck cancer Diseases 0.000 description 1
• SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 206010043207 temporal arteritis Diseases 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 229940126585 therapeutic drug Drugs 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 208000008732 thymoma Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 238000004448 titration 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
• 230000010474 transient expression Effects 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• 208000009174 transverse myelitis Diseases 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 208000029387 trophoblastic neoplasm Diseases 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 238000002255 vaccination Methods 0.000 description 1
• 206010046885 vaginal cancer Diseases 0.000 description 1
• 208000013139 vaginal neoplasm Diseases 0.000 description 1
• 244000052613 viral pathogen Species 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1