CA2155109A1 - Utilisation d'une composition pharmaceutique renfermant une quantite efficace d'interleukine-10, un analogue et (ou) un agoniste d'interleukine-10 - Google Patents
Utilisation d'une composition pharmaceutique renfermant une quantite efficace d'interleukine-10, un analogue et (ou) un agoniste d'interleukine-10Info
- Publication number
- CA2155109A1 CA2155109A1 CA002155109A CA2155109A CA2155109A1 CA 2155109 A1 CA2155109 A1 CA 2155109A1 CA 002155109 A CA002155109 A CA 002155109A CA 2155109 A CA2155109 A CA 2155109A CA 2155109 A1 CA2155109 A1 CA 2155109A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- medicament
- prevention
- diseases
- manufacture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000174 Interleukin-10 Proteins 0.000 title claims abstract description 31
- 102000003814 Interleukin-10 Human genes 0.000 title claims abstract description 28
- 229940076144 interleukin-10 Drugs 0.000 title claims abstract description 26
- 239000000556 agonist Substances 0.000 title claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 title description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 64
- 210000001616 monocyte Anatomy 0.000 claims abstract description 42
- 230000002947 procoagulating effect Effects 0.000 claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 claims abstract description 28
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims abstract description 23
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims abstract description 23
- 230000022023 interleukin-5 production Effects 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 21
- 230000004913 activation Effects 0.000 claims abstract description 19
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims abstract description 13
- 230000037361 pathway Effects 0.000 claims abstract description 13
- 102100022339 Integrin alpha-L Human genes 0.000 claims abstract description 9
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims abstract description 9
- 230000006806 disease prevention Effects 0.000 claims abstract description 7
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 4
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 claims abstract description 4
- 102000018594 Tumour necrosis factor Human genes 0.000 claims abstract 4
- 108050007852 Tumour necrosis factor Proteins 0.000 claims abstract 4
- 230000014509 gene expression Effects 0.000 claims description 50
- 108010002616 Interleukin-5 Proteins 0.000 claims description 40
- 108010000499 Thromboplastin Proteins 0.000 claims description 26
- 102000002262 Thromboplastin Human genes 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 206010040070 Septic Shock Diseases 0.000 claims description 18
- 230000006698 induction Effects 0.000 claims description 16
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 claims description 15
- 102000052620 human IL10 Human genes 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 15
- 230000036303 septic shock Effects 0.000 claims description 14
- 230000004044 response Effects 0.000 claims description 13
- 208000011580 syndromic disease Diseases 0.000 claims description 10
- 229930105110 Cyclosporin A Natural products 0.000 claims description 9
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 9
- 108010036949 Cyclosporine Proteins 0.000 claims description 9
- 206010014950 Eosinophilia Diseases 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- 229960001265 ciclosporin Drugs 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 claims description 3
- 230000001413 cellular effect Effects 0.000 claims description 3
- 210000003979 eosinophil Anatomy 0.000 claims description 3
- 108020001507 fusion proteins Proteins 0.000 claims description 3
- 102000037865 fusion proteins Human genes 0.000 claims description 3
- 208000024908 graft versus host disease Diseases 0.000 claims description 3
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 2
- 208000012657 Atopic disease Diseases 0.000 claims description 2
- 208000037157 Azotemia Diseases 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 claims description 2
- 206010006473 Bronchopulmonary aspergillosis Diseases 0.000 claims description 2
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 206010012441 Dermatitis bullous Diseases 0.000 claims description 2
- 206010012468 Dermatitis herpetiformis Diseases 0.000 claims description 2
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims description 2
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims description 2
- 206010015218 Erythema multiforme Diseases 0.000 claims description 2
- 208000015336 Helminthic disease Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 2
- 206010058858 Meningococcal bacteraemia Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000004430 Pulmonary Aspergillosis Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 206010051222 Toxic oil syndrome Diseases 0.000 claims description 2
- 206010065258 Tropical eosinophilia Diseases 0.000 claims description 2
- 206010047112 Vasculitides Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 2
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 2
- 230000002949 hemolytic effect Effects 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 229940125721 immunosuppressive agent Drugs 0.000 claims description 2
- 230000008595 infiltration Effects 0.000 claims description 2
- 238000001764 infiltration Methods 0.000 claims description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000008585 mastocytosis Diseases 0.000 claims description 2
- 208000022089 meningococcemia Diseases 0.000 claims description 2
- 238000012261 overproduction Methods 0.000 claims description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 2
- 229960002930 sirolimus Drugs 0.000 claims description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 229960004799 tryptophan Drugs 0.000 claims description 2
- 230000006433 tumor necrosis factor production Effects 0.000 claims description 2
- 208000009852 uremia Diseases 0.000 claims description 2
- 206010063094 Cerebral malaria Diseases 0.000 claims 2
- 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims 1
- 102100039897 Interleukin-5 Human genes 0.000 claims 1
- 201000009324 Loeffler syndrome Diseases 0.000 claims 1
- 201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims 1
- 208000013397 idiopathic acute eosinophilic pneumonia Diseases 0.000 claims 1
- 201000009732 pulmonary eosinophilia Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 90
- 230000000694 effects Effects 0.000 description 42
- 102000000743 Interleukin-5 Human genes 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 34
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 33
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 33
- 102000004127 Cytokines Human genes 0.000 description 31
- 108090000695 Cytokines Proteins 0.000 description 31
- 239000006228 supernatant Substances 0.000 description 30
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 29
- 238000002474 experimental method Methods 0.000 description 25
- 230000005764 inhibitory process Effects 0.000 description 25
- 239000013598 vector Substances 0.000 description 25
- 241000282414 Homo sapiens Species 0.000 description 24
- 239000002299 complementary DNA Substances 0.000 description 23
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 210000001165 lymph node Anatomy 0.000 description 20
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 19
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 19
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 17
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 17
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 17
- 210000002966 serum Anatomy 0.000 description 17
- 238000000034 method Methods 0.000 description 15
- 238000003752 polymerase chain reaction Methods 0.000 description 15
- 230000000735 allogeneic effect Effects 0.000 description 13
- 108020004999 messenger RNA Proteins 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000028327 secretion Effects 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 230000000284 resting effect Effects 0.000 description 12
- 230000001177 retroviral effect Effects 0.000 description 12
- 241001529936 Murinae Species 0.000 description 11
- 102000000588 Interleukin-2 Human genes 0.000 description 10
- 108010002350 Interleukin-2 Proteins 0.000 description 10
- 101001033265 Mus musculus Interleukin-10 Proteins 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 231100000225 lethality Toxicity 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 230000003472 neutralizing effect Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 210000000612 antigen-presenting cell Anatomy 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 238000011725 BALB/c mouse Methods 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 210000002950 fibroblast Anatomy 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 230000002631 hypothermal effect Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000011533 pre-incubation Methods 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 6
- 241000713858 Harvey murine sarcoma virus Species 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 108010092549 leukocyte procoagulant activity Proteins 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 210000004989 spleen cell Anatomy 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 230000003827 upregulation Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 206010053567 Coagulopathies Diseases 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 102100034343 Integrase Human genes 0.000 description 5
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000035602 clotting Effects 0.000 description 5
- 229940012413 factor vii Drugs 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 4
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
- 102100023804 Coagulation factor VII Human genes 0.000 description 4
- 108010023321 Factor VII Proteins 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 3
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 101150015560 IL5 gene Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 239000003710 calcium ionophore Substances 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 230000004940 costimulation Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 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 3
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 231100000617 superantigen Toxicity 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 208000037487 Endotoxemia Diseases 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100039068 Interleukin-10 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
- 241000239218 Limulus Species 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000011443 conventional therapy Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 2
- 238000011272 standard treatment Methods 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
- 239000000126 substance Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-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
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- RSGFPIWWSCWCFJ-VAXZQHAWSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O RSGFPIWWSCWCFJ-VAXZQHAWSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 108010045634 B7 Antigens Proteins 0.000 description 1
- 102000005738 B7 Antigens Human genes 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 101100075831 Caenorhabditis elegans mab-7 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010068051 Chimerism Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000027004 Eosinophilic disease Diseases 0.000 description 1
- 101100278327 Escherichia coli (strain K12) dosP gene Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000714188 Friend murine leukemia virus Species 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 238000002738 Giemsa staining Methods 0.000 description 1
- 206010051269 Graft thrombosis Diseases 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000002268 Hexosaminidases Human genes 0.000 description 1
- 108010000540 Hexosaminidases Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000996834 Homo sapiens Linker for activation of T-cells family member 2 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101150003028 Hprt1 gene Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 101150083678 IL2 gene Proteins 0.000 description 1
- 101150101999 IL6 gene Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102100034238 Linker for activation of T-cells family member 2 Human genes 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100438957 Mus musculus Cd8a gene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 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
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 101710182846 Polyhedrin Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 230000017274 T cell anergy Effects 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
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000024340 acute graft versus host disease Diseases 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 108010072542 endotoxin binding proteins Proteins 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229960002518 gentamicin Drugs 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
- 230000036541 health Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940100602 interleukin-5 Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000010841 mRNA extraction Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000005063 microvascular endothelium Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 238000001558 permutation test Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- -1 phosphoribosyl Chemical group 0.000 description 1
- 210000001698 popliteal fossa Anatomy 0.000 description 1
- 230000031915 positive regulation of coagulation Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5428—IL-10
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2066—IL-10
-
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP93400242.9 | 1993-02-01 | ||
| EP93400242 | 1993-02-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2155109A1 true CA2155109A1 (fr) | 1994-08-18 |
Family
ID=8214672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002155109A Abandoned CA2155109A1 (fr) | 1993-02-01 | 1994-02-01 | Utilisation d'une composition pharmaceutique renfermant une quantite efficace d'interleukine-10, un analogue et (ou) un agoniste d'interleukine-10 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0681589A1 (fr) |
| JP (1) | JPH08510719A (fr) |
| AU (1) | AU6000894A (fr) |
| CA (1) | CA2155109A1 (fr) |
| WO (1) | WO1994017773A2 (fr) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0756871A1 (fr) * | 1995-08-01 | 1997-02-05 | Institut Pasteur | Utilisation d'une composition pharmaceutique comprenant une dose efficace d'interleukine-10, d'un analogue et/ou d'un agoniste d'interleukine-10 |
| CA2228379A1 (fr) * | 1995-08-09 | 1997-02-20 | Schering Corporation | Utilisation combinee d'interleukine-10 et de cyclosporine pour une therapie immunosuppressive |
| US6022536A (en) * | 1995-08-09 | 2000-02-08 | Schering Corporation | Combined use of interleukin 10 and cyclosporin for immunosuppression therapy |
| WO1998026066A1 (fr) * | 1996-12-09 | 1998-06-18 | Ariad Gene Therapeutics, Inc. | Expression de proteines pour traiter l'asthme via l'activation, par ligand mediateur, de leurs genes de codage |
| EP1284747A2 (fr) | 2000-05-12 | 2003-02-26 | Beth Israel Deaconess Medical Center, Inc. | Compositions et procedes pour obtenir une suppression immune |
| GB0217777D0 (en) * | 2002-07-31 | 2002-09-11 | Novartis Ag | Organic compounds |
| WO2004050090A1 (fr) * | 2002-11-29 | 2004-06-17 | Maria Grazia Roncarolo | Rapamycine et il-10 pour le traitement de maladies auto-immunes |
| US7960355B2 (en) | 2003-05-23 | 2011-06-14 | Isis Pharmaceuticals, Inc. | Compositions and methods for the modulation of the expression of B7 protein |
| US7897582B2 (en) | 2003-05-23 | 2011-03-01 | Isis Pharmaceuticals, Inc. | Oligonucleotide compositions and methods for the modulation of the expression of B7 protein |
| RU2538613C2 (ru) * | 2012-10-11 | 2015-01-10 | Федеральное государственное бюджетное учреждение науки Институт теоретической и экспериментальной биофизики Российской академии наук | Интерлейкин-10, его применение и композиция на его основе для лечения нейродегенеративных процессов в мозге |
| MX2015014438A (es) | 2013-04-18 | 2016-05-18 | Armo Biosciences Inc | Metodos de uso de interleucina-10 para tratar enfermedades y trastornos. |
| EP3010527B1 (fr) | 2013-06-17 | 2018-08-08 | Armo Biosciences, Inc. | Méthode d'évaluation de l'identité et de la stabilité d'une protéine |
| CN105658232A (zh) | 2013-08-30 | 2016-06-08 | 阿尔莫生物科技股份有限公司 | 使用白细胞介素-10治疗疾病和病症的方法 |
| CN120242030A (zh) | 2013-11-11 | 2025-07-04 | 阿尔莫生物科技股份有限公司 | 将白细胞介素-10用于治疗疾病和病症的方法 |
| WO2015187295A2 (fr) | 2014-06-02 | 2015-12-10 | Armo Biosciences, Inc. | Méthodes permettant de faire baisser le cholestérol sérique |
| WO2016060996A2 (fr) | 2014-10-14 | 2016-04-21 | Armo Biosciences, Inc. | Compositions d'interleukine-15 et leurs utilisations |
| AU2015336101A1 (en) | 2014-10-22 | 2017-04-20 | Armo Biosciences, Inc. | Methods of using interleukin-10 for treating diseases and disorders |
| WO2016126615A1 (fr) | 2015-02-03 | 2016-08-11 | Armo Biosciences, Inc. | Procédés d'utilisation de l'interleukine-10 pour le traitement de maladies et de troubles |
| US20160361415A1 (en) | 2015-05-28 | 2016-12-15 | Armo Biosciences, Inc. | Methods of Using Interleukin-10 for Treating Diseases and Disorders |
| KR20180038553A (ko) | 2015-08-25 | 2018-04-16 | 아르모 바이오사이언시스 인코포레이티드 | 질환 및 장애를 치료하기 위한 인터류킨-10을 사용하는 방법 |
| JP6956950B2 (ja) * | 2016-12-27 | 2021-11-02 | 国立研究開発法人国立循環器病研究センター | リポソーム組成物及び炎症性疾患用治療剤 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU633034B2 (en) * | 1988-11-03 | 1993-01-21 | Schering Corporation | Method of preventing or reducing eosinophilia |
| IL94878A (en) * | 1989-06-28 | 2003-01-12 | Schering Corp | Cytokine synthesis inhibitory factor, antagonists thereof and methods of using same |
| DE4122402A1 (de) * | 1991-07-04 | 1993-01-07 | Schering Ag | Verwendung von interleukin 10 zur herstellung von arzneimitteln mit tumorhemmender wirksamkeit |
| EP0600970B1 (fr) * | 1991-08-06 | 1999-12-08 | Schering Corporation | Utilisation d'analogues ou d'antagonistes de l'interleukine-10 pour traiter la toxicite induite par l'endotoxine ou un superantigene |
| ZA931489B (en) * | 1992-03-04 | 1993-10-28 | Schering Corp | Use of interleuken-10 to suppress graft-vs-host disease |
| WO1993018783A1 (fr) * | 1992-03-20 | 1993-09-30 | Schering Corporation | Utilisation d'interleukine 10 pour induire la production d'antagoniste des recepteurs de l'interleukine 1 |
| RU2120802C1 (ru) * | 1992-08-20 | 1998-10-27 | Шеринг Корпорейшн | Фармацевтическая композиция, предназначенная для торможения зависимой от интерлейкина-2 пролиферации опухолевых клеток, увеличения содержания интерферона, лечения воспалительных заболеваний кишечника, потенцирования торможения производства цитокина и ограничения или торможения аллергической реакции замедленного типа |
-
1994
- 1994-02-01 WO PCT/EP1994/000283 patent/WO1994017773A2/fr not_active Ceased
- 1994-02-01 JP JP6517615A patent/JPH08510719A/ja active Pending
- 1994-02-01 EP EP94906191A patent/EP0681589A1/fr not_active Withdrawn
- 1994-02-01 CA CA002155109A patent/CA2155109A1/fr not_active Abandoned
- 1994-02-01 AU AU60008/94A patent/AU6000894A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1994017773A3 (fr) | 1994-12-22 |
| WO1994017773A2 (fr) | 1994-08-18 |
| JPH08510719A (ja) | 1996-11-12 |
| AU6000894A (en) | 1994-08-29 |
| EP0681589A1 (fr) | 1995-11-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2155109A1 (fr) | Utilisation d'une composition pharmaceutique renfermant une quantite efficace d'interleukine-10, un analogue et (ou) un agoniste d'interleukine-10 | |
| Salomon et al. | Tumor necrosis factor α and regulatory T cells in oncoimmunology | |
| Walzer et al. | Natural-killer cells and dendritic cells:“l'union fait la force” | |
| Cui et al. | Inhibition of T helper cell type 2 cell differentiation and immunoglobulin E response by ligand-activated Vα14 natural killer T cells | |
| Cerboni et al. | Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK-cell lysis | |
| Thomson et al. | New immunosuppressive drugs: mechanistic insights and potential therapeutic advances | |
| JP2883201B2 (ja) | Ｃｄ２８刺激関連免疫療法 | |
| Yang et al. | PD-L1 expression on human ocular cells and its possible role in regulating immune-mediated ocular inflammation | |
| Karimi et al. | NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT | |
| Chakraborty et al. | Complement after trauma: suturing innate and adaptive immunity | |
| Kim et al. | CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection: differential role of B7–1 in initiation versus progression of graft arteriosclerosis | |
| Nickerson et al. | Prolonged islet allograft acceptance in the absence of interleukin 4 expression | |
| SK21195A3 (en) | Pharmaceutical substance containing il-4 and/or il-10 or antibodies against il-4 and il-10, method of manufacture and use thereof | |
| SK288048B6 (sk) | Use of a substance effective in modulating signal transduction mediated by AILIM for suppressing, treating or preventing graft rejection and pharmaceutical composition comprising the substance for use in suppressing, treating or preventing graft rejection | |
| Benichou et al. | Innate immunity and resistance to tolerogenesis in allotransplantation | |
| Chong et al. | Immunobiologics in the treatment of psoriasis | |
| Stirling et al. | New immunological approaches and cytokine targets in asthma and allergy | |
| CA2253803A1 (fr) | Utilisation d'interleukine-10 pour produire une population de lymphocytes suppresseurs | |
| Laskowski et al. | Anti-CD28 monoclonal antibody therapy prevents chronic rejection of renal allografts in rats | |
| Arai et al. | Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection | |
| Lu et al. | Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603 | |
| Bullens et al. | Effects of co-stimulation by CD58 on human T cell cytokine production: a selective cytokine pattern with induction of high IL-10 production | |
| US20250099542A1 (en) | Method of treating a tumor with a combination of il-7 protein and vegf antagonist | |
| Taylor et al. | Analysis of the requirements for the induction of CD4+ T cell alloantigen hyporesponsiveness by ex vivo anti-CD40 ligand antibody | |
| Green et al. | T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA‐1‐mediated events |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |