EA039303B1 - Антитела, направленные на cd127 - Google Patents
Антитела, направленные на cd127 Download PDFInfo
- Publication number
- EA039303B1 EA039303B1 EA201692460A EA201692460A EA039303B1 EA 039303 B1 EA039303 B1 EA 039303B1 EA 201692460 A EA201692460 A EA 201692460A EA 201692460 A EA201692460 A EA 201692460A EA 039303 B1 EA039303 B1 EA 039303B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- seq
- antibody
- sequence
- cells
- human
- Prior art date
Links
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 claims abstract description 354
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 claims abstract description 295
- 210000004027 cell Anatomy 0.000 claims abstract description 260
- 108010002586 Interleukin-7 Proteins 0.000 claims abstract description 146
- 241000282414 Homo sapiens Species 0.000 claims abstract description 133
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 claims abstract description 119
- 210000004443 dendritic cell Anatomy 0.000 claims abstract description 59
- 102000049284 human IL7R Human genes 0.000 claims abstract description 58
- 230000035800 maturation Effects 0.000 claims abstract description 44
- 239000005557 antagonist Substances 0.000 claims abstract description 14
- 230000019491 signal transduction Effects 0.000 claims abstract description 9
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 claims abstract description 5
- 230000027455 binding Effects 0.000 claims description 193
- 239000000427 antigen Substances 0.000 claims description 186
- 102000036639 antigens Human genes 0.000 claims description 186
- 108091007433 antigens Proteins 0.000 claims description 186
- 239000012634 fragment Substances 0.000 claims description 173
- 229920002521 macromolecule Polymers 0.000 claims description 129
- 150000001413 amino acids Chemical class 0.000 claims description 125
- 230000014509 gene expression Effects 0.000 claims description 116
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 81
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 80
- 238000000034 method Methods 0.000 claims description 78
- 238000011282 treatment Methods 0.000 claims description 57
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 52
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 230000005764 inhibitory process Effects 0.000 claims description 42
- 201000010099 disease Diseases 0.000 claims description 40
- 150000007523 nucleic acids Chemical class 0.000 claims description 32
- 102000039446 nucleic acids Human genes 0.000 claims description 31
- 108020004707 nucleic acids Proteins 0.000 claims description 31
- 238000004519 manufacturing process Methods 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 108091033319 polynucleotide Proteins 0.000 claims description 30
- 102000040430 polynucleotide Human genes 0.000 claims description 30
- 239000002157 polynucleotide Substances 0.000 claims description 30
- 101000978362 Homo sapiens C-C motif chemokine 17 Proteins 0.000 claims description 26
- 102100023698 C-C motif chemokine 17 Human genes 0.000 claims description 25
- 230000011664 signaling Effects 0.000 claims description 21
- 230000026731 phosphorylation Effects 0.000 claims description 20
- 238000006366 phosphorylation reaction Methods 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 208000023275 Autoimmune disease Diseases 0.000 claims description 16
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 238000002054 transplantation Methods 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 15
- 230000003042 antagnostic effect Effects 0.000 claims description 13
- 230000003211 malignant effect Effects 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 12
- 230000003053 immunization Effects 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- 208000026935 allergic disease Diseases 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 10
- 229920001184 polypeptide Polymers 0.000 claims description 10
- 208000023504 respiratory system disease Diseases 0.000 claims description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 206010025323 Lymphomas Diseases 0.000 claims description 8
- 230000001363 autoimmune Effects 0.000 claims description 8
- 230000033581 fucosylation Effects 0.000 claims description 7
- 208000032839 leukemia Diseases 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 6
- 208000036142 Viral infection Diseases 0.000 claims description 5
- 206010025135 lupus erythematosus Diseases 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- 241000271566 Aves Species 0.000 claims description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 201000002491 encephalomyelitis Diseases 0.000 claims description 4
- 230000002519 immonomodulatory effect Effects 0.000 claims description 4
- 238000011160 research Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 102100021592 Interleukin-7 Human genes 0.000 claims 7
- 108040006861 interleukin-7 receptor activity proteins Proteins 0.000 claims 4
- 238000011835 investigation Methods 0.000 claims 2
- 238000011084 recovery Methods 0.000 claims 2
- 102000001712 STAT5 Transcription Factor Human genes 0.000 claims 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 claims 1
- 102000000704 Interleukin-7 Human genes 0.000 abstract description 139
- 229940100994 interleukin-7 Drugs 0.000 abstract description 135
- 102000005962 receptors Human genes 0.000 abstract description 45
- 108020003175 receptors Proteins 0.000 abstract description 45
- 230000003993 interaction Effects 0.000 abstract description 34
- 230000001472 cytotoxic effect Effects 0.000 abstract description 16
- 230000008506 pathogenesis Effects 0.000 abstract description 4
- 102000004127 Cytokines Human genes 0.000 abstract description 3
- 108090000695 Cytokines Proteins 0.000 abstract description 3
- 230000000139 costimulatory effect Effects 0.000 abstract description 3
- 230000003827 upregulation Effects 0.000 abstract description 2
- 108010029307 thymic stromal lymphopoietin Proteins 0.000 description 115
- 235000001014 amino acid Nutrition 0.000 description 114
- 102000010782 Interleukin-7 Receptors Human genes 0.000 description 49
- 108010038498 Interleukin-7 Receptors Proteins 0.000 description 49
- 241000700159 Rattus Species 0.000 description 49
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 46
- 230000000694 effects Effects 0.000 description 44
- 102100038497 Cytokine receptor-like factor 2 Human genes 0.000 description 43
- 101710194733 Cytokine receptor-like factor 2 Proteins 0.000 description 43
- 241001465754 Metazoa Species 0.000 description 42
- 108090000623 proteins and genes Proteins 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 33
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 31
- 235000018102 proteins Nutrition 0.000 description 31
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 30
- 238000002347 injection Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 24
- 101150013553 CD40 gene Proteins 0.000 description 22
- 241000699670 Mus sp. Species 0.000 description 22
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 22
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 22
- 238000003556 assay Methods 0.000 description 22
- 238000003776 cleavage reaction Methods 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 230000007017 scission Effects 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 21
- 230000001965 increasing effect Effects 0.000 description 21
- 210000003071 memory t lymphocyte Anatomy 0.000 description 19
- 238000005516 engineering process Methods 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 17
- 102000006495 integrins Human genes 0.000 description 17
- 108010044426 integrins Proteins 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000011534 incubation Methods 0.000 description 16
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 15
- 101001043807 Homo sapiens Interleukin-7 Proteins 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 15
- 102000052622 human IL7 Human genes 0.000 description 15
- 210000004408 hybridoma Anatomy 0.000 description 15
- 239000003446 ligand Substances 0.000 description 15
- 210000003289 regulatory T cell Anatomy 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- 238000002965 ELISA Methods 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 230000037361 pathway Effects 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000000749 co-immunoprecipitation Methods 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 230000004041 dendritic cell maturation Effects 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 230000028993 immune response Effects 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 9
- 102000003992 Peroxidases Human genes 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000004069 differentiation Effects 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 9
- 238000002649 immunization Methods 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 210000004698 lymphocyte Anatomy 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 108040007629 peroxidase activity proteins Proteins 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 239000012636 effector Substances 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 210000002865 immune cell Anatomy 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 210000000822 natural killer cell Anatomy 0.000 description 8
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 7
- 108090000317 Chymotrypsin Proteins 0.000 description 7
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 7
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 7
- 241000282520 Papio Species 0.000 description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 229960002376 chymotrypsin Drugs 0.000 description 7
- 206010009887 colitis Diseases 0.000 description 7
- 231100000433 cytotoxic Toxicity 0.000 description 7
- 210000003162 effector t lymphocyte Anatomy 0.000 description 7
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 210000000265 leukocyte Anatomy 0.000 description 7
- 238000004949 mass spectrometry Methods 0.000 description 7
- 230000003278 mimic effect Effects 0.000 description 7
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 7
- 230000006798 recombination Effects 0.000 description 7
- 238000005215 recombination Methods 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 229960000074 biopharmaceutical Drugs 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002163 immunogen Effects 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 238000002493 microarray Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000004580 weight loss Effects 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 241000283074 Equus asinus Species 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 241000282516 Papio anubis Species 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 210000001072 colon Anatomy 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000033300 receptor internalization Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000000717 retained effect Effects 0.000 description 5
- 210000000813 small intestine Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000001541 thymus gland Anatomy 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 206010015150 Erythema Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 4
- 102000007440 Interleukin-7 Receptor alpha Subunit Human genes 0.000 description 4
- 108010086134 Interleukin-7 Receptor alpha Subunit Proteins 0.000 description 4
- 201000003791 MALT lymphoma Diseases 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 102000003675 cytokine receptors Human genes 0.000 description 4
- 108010057085 cytokine receptors Proteins 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 231100000321 erythema Toxicity 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 208000024908 graft versus host disease Diseases 0.000 description 4
- 239000000833 heterodimer Substances 0.000 description 4
- 230000002871 immunocytoma Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 229960001005 tuberculin Drugs 0.000 description 4
- 230000005951 type IV hypersensitivity Effects 0.000 description 4
- 239000011534 wash buffer Substances 0.000 description 4
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 3
- 238000012286 ELISA Assay Methods 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 3
- 108010024121 Janus Kinases Proteins 0.000 description 3
- 102000015617 Janus Kinases Human genes 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical group SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 3
- 108091007960 PI3Ks Proteins 0.000 description 3
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 3
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 101000844753 Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770) DNA-binding protein 7d Proteins 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 101150117115 V gene Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 230000020411 cell activation Effects 0.000 description 3
- 239000002458 cell surface marker Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 238000011577 humanized mouse model Methods 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000000126 in silico method Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000000074 matrix-assisted laser desorption--ionisation tandem time-of-flight detection Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 210000002501 natural regulatory T cell Anatomy 0.000 description 3
- 230000011234 negative regulation of signal transduction Effects 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 230000006320 pegylation Effects 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000008054 signal transmission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- 101100152731 Arabidopsis thaliana TH2 gene Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 206010057248 Cell death Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 2
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 206010025327 Lymphopenia Diseases 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 230000000961 alloantigen Effects 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000009830 antibody antigen interaction Effects 0.000 description 2
- 210000000628 antibody-producing cell Anatomy 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 210000001723 extracellular space Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 231100001023 lymphopenia Toxicity 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 238000002702 ribosome display Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- -1 succinimide ester Chemical class 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- QSSAZDNARJWYEF-UHFFFAOYSA-N 1-(dibromomethyl)-2-methylbenzene Chemical group CC1=CC=CC=C1C(Br)Br QSSAZDNARJWYEF-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 102220510016 52 kDa repressor of the inhibitor of the protein kinase_V54I_mutation Human genes 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 108010035053 B7-1 Antigen Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- 108010063916 CD40 Antigens Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010082169 Chemokine CCL17 Proteins 0.000 description 1
- 102000003826 Chemokine CCL17 Human genes 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 208000006968 Helminthiasis Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001002508 Homo sapiens Immunoglobulin-binding protein 1 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001008922 Homo sapiens Kallikrein-11 Proteins 0.000 description 1
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 101000716124 Homo sapiens T-cell surface glycoprotein CD1c Proteins 0.000 description 1
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102100021042 Immunoglobulin-binding protein 1 Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102100027612 Kallikrein-11 Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 125000000415 L-cysteinyl group Chemical group O=C([*])[C@@](N([H])[H])([H])C([H])([H])S[H] 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 102000019298 Lipocalin Human genes 0.000 description 1
- 108050006654 Lipocalin Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 1
- 101001043810 Macaca fascicularis Interleukin-7 receptor subunit alpha Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 231100000742 Plant toxin Toxicity 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 108700033844 Pseudomonas aeruginosa toxA Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101710146873 Receptor-binding protein Proteins 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 108010072819 STAT Transcription Factors Proteins 0.000 description 1
- 102000007078 STAT Transcription Factors Human genes 0.000 description 1
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 1
- 102000006381 STAT1 Transcription Factor Human genes 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 108010084592 Saporins Proteins 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 241000205098 Sulfolobus acidocaldarius Species 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 102220536881 Transcription factor JunD_Y77F_mutation Human genes 0.000 description 1
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108010082017 alpha chain interleukin-7 receptor Proteins 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 108700000707 bcl-2-Associated X Proteins 0.000 description 1
- 102000055102 bcl-2-Associated X Human genes 0.000 description 1
- 108010007734 bcl-Associated Death Protein Proteins 0.000 description 1
- 102000007348 bcl-Associated Death Protein Human genes 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 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 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 208000018805 childhood acute lymphoblastic leukemia Diseases 0.000 description 1
- 201000011633 childhood acute lymphocytic leukemia Diseases 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000008951 colonic inflammation Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 238000012926 crystallographic analysis Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 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
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 102000044739 human CD1C Human genes 0.000 description 1
- 102000045535 human TSLP Human genes 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 210000003297 immature b lymphocyte Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 210000000428 immunological synapse Anatomy 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 108010021315 integrin beta7 Proteins 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000008944 intestinal immunity Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 208000014837 parasitic helminthiasis infectious disease Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000003123 plant toxin Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 102220212795 rs1060501982 Human genes 0.000 description 1
- 102220065731 rs140562402 Human genes 0.000 description 1
- 102220011217 rs281865122 Human genes 0.000 description 1
- 102200026976 rs35086888 Human genes 0.000 description 1
- 102220058924 rs749212640 Human genes 0.000 description 1
- 102220340177 rs782563826 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 230000023441 thymic stromal lymphopoietin production Effects 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/5418—IL-7
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70546—Integrin superfamily, e.g. VLAs, leuCAM, GPIIb/GPIIIa, LPAM
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
- G01N2333/7155—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462010117P | 2014-06-10 | 2014-06-10 | |
| EP15305078.6A EP2955196A1 (en) | 2014-06-10 | 2015-01-23 | Antibodies directed against CD127 |
| PCT/EP2015/062993 WO2015189302A1 (en) | 2014-06-10 | 2015-06-10 | Antibodies directed against cd127 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201692460A1 EA201692460A1 (ru) | 2017-04-28 |
| EA039303B1 true EA039303B1 (ru) | 2022-01-11 |
Family
ID=52434718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201692460A EA039303B1 (ru) | 2014-06-10 | 2015-06-10 | Антитела, направленные на cd127 |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US10428152B2 (enExample) |
| EP (2) | EP2955196A1 (enExample) |
| JP (2) | JP7324565B2 (enExample) |
| KR (1) | KR102612930B1 (enExample) |
| CN (1) | CN106715471B (enExample) |
| AP (1) | AP2016009599A0 (enExample) |
| AU (1) | AU2015273532C1 (enExample) |
| BR (1) | BR112016028755B1 (enExample) |
| CA (1) | CA2950823A1 (enExample) |
| CL (1) | CL2016003172A1 (enExample) |
| CR (1) | CR20160576A (enExample) |
| EA (1) | EA039303B1 (enExample) |
| HK (1) | HK1231487A1 (enExample) |
| IL (1) | IL249449B (enExample) |
| MA (1) | MA40202A (enExample) |
| MX (1) | MX376066B (enExample) |
| MY (1) | MY190889A (enExample) |
| NZ (1) | NZ726932A (enExample) |
| PE (1) | PE20170324A1 (enExample) |
| PH (1) | PH12016502445A1 (enExample) |
| RU (1) | RU2734076C2 (enExample) |
| SA (1) | SA516380455B1 (enExample) |
| SG (1) | SG11201610036PA (enExample) |
| TN (1) | TN2016000528A1 (enExample) |
| UA (1) | UA125366C2 (enExample) |
| WO (1) | WO2015189302A1 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201404991YA (en) | 2012-02-23 | 2014-09-26 | Stage Cell Therapeutics Gmbh | Chromatographic isolation of cells and other complex biological materials |
| EP2955196A1 (en) * | 2014-06-10 | 2015-12-16 | Effimune | Antibodies directed against CD127 |
| HK1250040A1 (zh) | 2015-03-31 | 2018-11-23 | Sorriso Pharmaceuticals, Inc. | 多肽 |
| CA2981098A1 (en) | 2015-03-31 | 2016-10-06 | Vhsquared Limited | Peptide construct having a protease-cleavable linker |
| MA45488A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés, kits et appareil de culture de cellules |
| WO2017125578A1 (en) | 2016-01-21 | 2017-07-27 | Vhsquared Limited | Polypeptides |
| SMT201900460T1 (it) * | 2016-02-29 | 2019-09-09 | Ose Immunotherapeutics | Anticorpi non antagonisti diretti contro la catena alfa del dominio extracellulare del recettore di il17 e loro uso nel trattamento del cancro |
| MY190770A (en) * | 2016-12-09 | 2022-05-12 | Ose Immunotherapeutics | Antibodies and polypeptides directed against cd127 |
| WO2019043065A1 (en) * | 2017-08-29 | 2019-03-07 | Ose Immunotherapeutics | METHOD AND PREPARATION FOR SORTING T EFFECTOR LYMPHOCYTES USING ANTI-CD127 ANTIBODIES FOR CELL THERAPY APPLICATIONS |
| CN110117325B (zh) * | 2018-03-09 | 2023-06-20 | 重庆市畜牧科学院 | 一种猪cd127多肽及其编码基因和应用 |
| US11008395B2 (en) | 2019-01-22 | 2021-05-18 | Bristol Myers-Squibb Company | Antibodies against IL-7R alpha subunit and uses thereof |
| KR102503349B1 (ko) | 2019-05-14 | 2023-02-23 | 프로벤션 바이오, 인코포레이티드 | 제1형 당뇨병을 예방하기 위한 방법 및 조성물 |
| AU2020294980A1 (en) * | 2019-06-21 | 2022-02-17 | Sorriso Pharmaceuticals, Inc. | Polypeptides |
| EP3986931A1 (en) | 2019-06-21 | 2022-04-27 | Sorriso Pharmaceuticals, Inc. | Polypeptides |
| MX2021015762A (es) | 2019-06-21 | 2022-04-18 | Sorriso Pharmaceuticals Inc | Composiciones. |
| CN110894237B (zh) * | 2019-12-05 | 2021-08-03 | 山东省分析测试中心 | 抗cd127的抗体、分泌该抗体的细胞株及其制备方法和应用 |
| WO2021222227A1 (en) * | 2020-04-27 | 2021-11-04 | Memorial Sloan-Kettering Cancer Center | Chimeric antigen receptors targeting cd127 and use thereof |
| US12006366B2 (en) | 2020-06-11 | 2024-06-11 | Provention Bio, Inc. | Methods and compositions for preventing type 1 diabetes |
| US20220389104A1 (en) | 2021-05-28 | 2022-12-08 | Ose Immunotherapeutics | Method for Treating CD127-Positive Cancers by Administering an Anti-CD127 Agent |
| CA3250546A1 (en) | 2022-05-30 | 2023-12-07 | Ose Immunotherapeutics | IL7R MODULATOR ACTIVITY BIOMARKERS |
| CN115925955B (zh) * | 2022-12-30 | 2025-09-26 | 浙江正熙生物技术有限公司 | 一种抗cd127抗体及其制备方法和应用 |
| WO2024146955A1 (en) | 2023-01-06 | 2024-07-11 | Twain Therapeutics Pte. Ltd. | Antigen-binding molecules |
| EP4455308A1 (en) | 2023-04-24 | 2024-10-30 | Les Laboratoires Servier | Il-7r gene signatures |
| US12311033B2 (en) | 2023-05-31 | 2025-05-27 | Capstan Therapeutics, Inc. | Lipid nanoparticle formulations and compositions |
| WO2025076113A1 (en) | 2023-10-05 | 2025-04-10 | Capstan Therapeutics, Inc. | Ionizable cationic lipids with conserved spacing and lipid nanoparticles |
| US20250127728A1 (en) | 2023-10-05 | 2025-04-24 | Capstan Therapeutics, Inc. | Constrained Ionizable Cationic Lipids and Lipid Nanoparticles |
| WO2025089399A1 (ja) * | 2023-10-26 | 2025-05-01 | 国立研究開発法人国立がん研究センター | インターロイキン７受容体（ｉｌ－７ｒ）に対する抗体および当該抗体を含む抗体薬物コンジュゲート（ａｄｃ） |
| US20250302763A1 (en) | 2024-02-22 | 2025-10-02 | Capstan Therapeutics, Inc. | Immune engineering amplification |
| WO2025202213A1 (en) | 2024-03-26 | 2025-10-02 | Institut National de la Santé et de la Recherche Médicale | Lipid nanoparticle loaded with antitumoral agent and functionnalized to target immosuppressive cells |
| WO2025217454A2 (en) | 2024-04-11 | 2025-10-16 | Capstan Therapeutics, Inc. | Ionizable cationic lipids and lipid nanoparticles |
| WO2025217452A1 (en) | 2024-04-11 | 2025-10-16 | Capstan Therapeutics, Inc. | Constrained ionizable cationic lipids and lipid nanoparticles |
| CN118638236B (zh) * | 2024-07-09 | 2025-03-14 | 武汉爱博泰克生物科技有限公司 | 抗人cd127蛋白的抗体、抗体偶联物及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011094259A2 (en) * | 2010-01-28 | 2011-08-04 | Glaxo Group Limited | Cd127 binding proteins |
| WO2011104687A1 (en) * | 2010-02-24 | 2011-09-01 | Rinat Neuroscience Corporation | Antagonist anti-il-7 receptor antibodies and methods |
| WO2013056984A1 (en) * | 2011-10-19 | 2013-04-25 | Effimune | Antibodies directed against the alpha chain of il7 receptor - their use for the preparation of drug candidates |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| CA2655392A1 (en) | 2006-05-31 | 2007-12-06 | The Regents Of The University Of California | Cd127 expression inversely correlates with foxp3 and suppressive function of cd4+ tregs |
| EP1930342B1 (en) | 2006-12-04 | 2012-01-25 | Institut Pasteur | OB-fold used as scaffold for engineering new specific binders |
| TW201018482A (en) * | 2008-08-08 | 2010-05-16 | Glaxo Wellcome Mfg Pte Ltd | Novel treatment |
| WO2010085643A1 (en) | 2009-01-22 | 2010-07-29 | University Of Miami | Targeting il-7 signaling as a therapy for multiple sclerosis and other il-7 signaling dependent disorders |
| EP2955196A1 (en) * | 2014-06-10 | 2015-12-16 | Effimune | Antibodies directed against CD127 |
| SMT201900460T1 (it) | 2016-02-29 | 2019-09-09 | Ose Immunotherapeutics | Anticorpi non antagonisti diretti contro la catena alfa del dominio extracellulare del recettore di il17 e loro uso nel trattamento del cancro |
-
2015
- 2015-01-23 EP EP15305078.6A patent/EP2955196A1/en not_active Withdrawn
- 2015-06-10 KR KR1020177000724A patent/KR102612930B1/ko active Active
- 2015-06-10 BR BR112016028755-0A patent/BR112016028755B1/pt active IP Right Grant
- 2015-06-10 PE PE2016002699A patent/PE20170324A1/es unknown
- 2015-06-10 MX MX2016016236A patent/MX376066B/es active IP Right Grant
- 2015-06-10 HK HK17104912.8A patent/HK1231487A1/zh unknown
- 2015-06-10 RU RU2016151265A patent/RU2734076C2/ru active
- 2015-06-10 AP AP2016009599A patent/AP2016009599A0/en unknown
- 2015-06-10 EA EA201692460A patent/EA039303B1/ru unknown
- 2015-06-10 NZ NZ726932A patent/NZ726932A/en unknown
- 2015-06-10 CR CR20160576A patent/CR20160576A/es unknown
- 2015-06-10 MY MYPI2016002094A patent/MY190889A/en unknown
- 2015-06-10 MA MA040202A patent/MA40202A/fr unknown
- 2015-06-10 JP JP2017517406A patent/JP7324565B2/ja active Active
- 2015-06-10 EP EP15727989.4A patent/EP3155014A1/en active Pending
- 2015-06-10 AU AU2015273532A patent/AU2015273532C1/en active Active
- 2015-06-10 WO PCT/EP2015/062993 patent/WO2015189302A1/en not_active Ceased
- 2015-06-10 TN TN2016000528A patent/TN2016000528A1/en unknown
- 2015-06-10 US US15/317,355 patent/US10428152B2/en active Active
- 2015-06-10 CA CA2950823A patent/CA2950823A1/en active Pending
- 2015-06-10 CN CN201580043066.1A patent/CN106715471B/zh active Active
- 2015-06-10 SG SG11201610036PA patent/SG11201610036PA/en unknown
- 2015-06-10 UA UAA201613258A patent/UA125366C2/uk unknown
-
2016
- 2016-12-06 PH PH12016502445A patent/PH12016502445A1/en unknown
- 2016-12-07 IL IL249449A patent/IL249449B/en active IP Right Grant
- 2016-12-08 SA SA516380455A patent/SA516380455B1/ar unknown
- 2016-12-09 CL CL2016003172A patent/CL2016003172A1/es unknown
-
2019
- 2019-08-05 US US16/532,000 patent/US11440964B2/en active Active
-
2021
- 2021-08-05 JP JP2021128846A patent/JP2021184731A/ja active Pending
-
2022
- 2022-09-09 US US17/941,885 patent/US12371502B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011094259A2 (en) * | 2010-01-28 | 2011-08-04 | Glaxo Group Limited | Cd127 binding proteins |
| WO2011104687A1 (en) * | 2010-02-24 | 2011-09-01 | Rinat Neuroscience Corporation | Antagonist anti-il-7 receptor antibodies and methods |
| WO2013056984A1 (en) * | 2011-10-19 | 2013-04-25 | Effimune | Antibodies directed against the alpha chain of il7 receptor - their use for the preparation of drug candidates |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12371502B2 (en) | Antibodies directed against CD127 | |
| US11945861B2 (en) | Human anti-IFN-α antibodies | |
| EP3708582A1 (en) | 4-1bb antibody and preparation method and use thereof | |
| JP7179743B2 (ja) | 抗ＳＩＲＰｇ抗体の新規の使用 | |
| JP2022169504A (ja) | 新規な抗ＳＩＲＰａ抗体およびそれらの治療適用 | |
| US11230602B2 (en) | Non-antagonistic antibodies directed against the alpha chain of the IL7 receptor extracellular domain and use thereof in cancer treatment | |
| OA20097A (en) | Antibodies directed against CD127. | |
| CN118852427A (zh) | 靶向cd70的单克隆抗体及其用途 | |
| HK40000684B (en) | Non-antagonistic antibodies directed against the alpha chain of the il7 receptor extracellular domain and use thereof in cancer treatment | |
| HK40000684A (en) | Non-antagonistic antibodies directed against the alpha chain of the il7 receptor extracellular domain and use thereof in cancer treatment | |
| HK1219961B (en) | Human anti-ifn-alpha antibodies |