WO2000056356A2 - Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (gcs) - Google Patents
Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (gcs) Download PDFInfo
- Publication number
- WO2000056356A2 WO2000056356A2 PCT/US2000/007959 US0007959W WO0056356A2 WO 2000056356 A2 WO2000056356 A2 WO 2000056356A2 US 0007959 W US0007959 W US 0007959W WO 0056356 A2 WO0056356 A2 WO 0056356A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- apcs
- cells
- antigen
- gcs
- composition
- Prior art date
Links
- 102000036639 antigens Human genes 0.000 title claims abstract description 119
- 108091007433 antigens Proteins 0.000 title claims abstract description 118
- 239000000427 antigen Substances 0.000 title claims abstract description 117
- 208000005017 glioblastoma Diseases 0.000 title claims abstract description 31
- 239000012228 culture supernatant Substances 0.000 title claims description 19
- 230000006698 induction Effects 0.000 title description 3
- 210000004027 cell Anatomy 0.000 claims abstract description 135
- 210000000612 antigen-presenting cell Anatomy 0.000 claims abstract description 122
- 210000001616 monocyte Anatomy 0.000 claims abstract description 111
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 98
- 238000000034 method Methods 0.000 claims abstract description 73
- 239000000203 mixture Substances 0.000 claims abstract description 60
- 230000028993 immune response Effects 0.000 claims abstract description 56
- 210000004443 dendritic cell Anatomy 0.000 claims abstract description 38
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 31
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 31
- 230000001506 immunosuppresive effect Effects 0.000 claims abstract description 27
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 19
- 230000005764 inhibitory process Effects 0.000 claims abstract description 19
- 230000000599 auto-anti-genic effect Effects 0.000 claims abstract description 17
- 206010011968 Decreased immune responsiveness Diseases 0.000 claims abstract description 14
- 230000006907 apoptotic process Effects 0.000 claims abstract description 13
- 210000002540 macrophage Anatomy 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 108010065805 Interleukin-12 Proteins 0.000 claims description 44
- 102000013462 Interleukin-12 Human genes 0.000 claims description 44
- 238000004519 manufacturing process Methods 0.000 claims description 39
- 230000000694 effects Effects 0.000 claims description 32
- 102000003814 Interleukin-10 Human genes 0.000 claims description 30
- 108090000174 Interleukin-10 Proteins 0.000 claims description 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 108090001005 Interleukin-6 Proteins 0.000 claims description 23
- 239000006228 supernatant Substances 0.000 claims description 22
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 claims description 21
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 claims description 20
- 230000002829 reductive effect Effects 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 16
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 230000035755 proliferation Effects 0.000 claims description 16
- 102000043131 MHC class II family Human genes 0.000 claims description 12
- 108091054438 MHC class II family Proteins 0.000 claims description 12
- 238000011534 incubation Methods 0.000 claims description 12
- 206010028417 myasthenia gravis Diseases 0.000 claims description 12
- 230000009467 reduction Effects 0.000 claims description 12
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 claims description 11
- 230000003247 decreasing effect Effects 0.000 claims description 11
- 230000004044 response Effects 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 8
- 238000001114 immunoprecipitation Methods 0.000 claims description 8
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 8
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 7
- 102000034337 acetylcholine receptors Human genes 0.000 claims description 7
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 7
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 6
- 102000004142 Trypsin Human genes 0.000 claims description 6
- 108090000631 Trypsin Proteins 0.000 claims description 6
- 238000004113 cell culture Methods 0.000 claims description 6
- 239000012588 trypsin Substances 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 102000007079 Peptide Fragments Human genes 0.000 claims description 4
- 108010033276 Peptide Fragments Proteins 0.000 claims description 4
- 238000005341 cation exchange Methods 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- 102000000503 Collagen Type II Human genes 0.000 claims description 3
- 108010041390 Collagen Type II Proteins 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 210000004153 islets of langerhan Anatomy 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 102000007999 Nuclear Proteins Human genes 0.000 claims description 2
- 108010089610 Nuclear Proteins Proteins 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 210000001787 dendrite Anatomy 0.000 claims 4
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 238000002054 transplantation Methods 0.000 abstract description 5
- 230000008105 immune reaction Effects 0.000 abstract description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 75
- 108010047620 Phytohemagglutinins Proteins 0.000 description 29
- 238000002474 experimental method Methods 0.000 description 29
- 230000001885 phytohemagglutinin Effects 0.000 description 29
- 102000004127 Cytokines Human genes 0.000 description 23
- 108090000695 Cytokines Proteins 0.000 description 23
- 238000011282 treatment Methods 0.000 description 23
- 102000004889 Interleukin-6 Human genes 0.000 description 22
- 102100037850 Interferon gamma Human genes 0.000 description 20
- 108010074328 Interferon-gamma Proteins 0.000 description 20
- CZCIKBSVHDNIDH-UHFFFAOYSA-N Nalpha-methyl-DL-tryptophan Natural products C1=CC=C2C(CC(NC)C(O)=O)=CNC2=C1 CZCIKBSVHDNIDH-UHFFFAOYSA-N 0.000 description 19
- 238000010790 dilution Methods 0.000 description 19
- 239000012895 dilution Substances 0.000 description 19
- 230000031261 interleukin-10 production Effects 0.000 description 19
- 230000000638 stimulation Effects 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- 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 16
- 210000004989 spleen cell Anatomy 0.000 description 15
- 102000004388 Interleukin-4 Human genes 0.000 description 14
- 108090000978 Interleukin-4 Proteins 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 14
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 13
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 13
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 13
- ZADWXFSZEAPBJS-JTQLQIEISA-N 1-methyl-L-tryptophan Chemical compound C1=CC=C2N(C)C=C(C[C@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-JTQLQIEISA-N 0.000 description 12
- 206010018338 Glioma Diseases 0.000 description 12
- 230000033540 T cell apoptotic process Effects 0.000 description 12
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 12
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 12
- ZADWXFSZEAPBJS-UHFFFAOYSA-N racemic N-methyl tryptophan Natural products C1=CC=C2N(C)C=C(CC(N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-UHFFFAOYSA-N 0.000 description 12
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
- 230000006052 T cell proliferation Effects 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 230000019734 interleukin-12 production Effects 0.000 description 11
- 208000032612 Glial tumor Diseases 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 102000015696 Interleukins Human genes 0.000 description 9
- 108010063738 Interleukins Proteins 0.000 description 9
- 102000047918 Myelin Basic Human genes 0.000 description 9
- 101710107068 Myelin basic protein Proteins 0.000 description 9
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000011533 pre-incubation Methods 0.000 description 9
- 238000002203 pretreatment Methods 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 8
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- 230000004069 differentiation Effects 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 229960000814 tetanus toxoid Drugs 0.000 description 8
- 238000011740 C57BL/6 mouse Methods 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 239000012980 RPMI-1640 medium Substances 0.000 description 7
- 230000016396 cytokine production Effects 0.000 description 7
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
- 239000003226 mitogen Substances 0.000 description 7
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 6
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 230000003915 cell function Effects 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 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 6
- 241000712431 Influenza A virus Species 0.000 description 5
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 5
- 108091008874 T cell receptors Proteins 0.000 description 5
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 206010022000 influenza Diseases 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 4
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000043129 MHC class I family Human genes 0.000 description 4
- 108091054437 MHC class I family Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000002523 gelfiltration Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000004957 immunoregulator effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000004073 interleukin-2 production Effects 0.000 description 4
- 230000017306 interleukin-6 production Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 230000009696 proliferative response Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- 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 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 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 3
- 230000006044 T cell activation Effects 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 3
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 3
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- 108050006400 Cyclin Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 2
- 108010075704 HLA-A Antigens Proteins 0.000 description 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101100456320 Homo sapiens NR3C2 gene Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 102000000743 Interleukin-5 Human genes 0.000 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 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 239000012505 Superdex™ Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003092 anti-cytokine Effects 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000006472 autoimmune response Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 230000007969 cellular immunity Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229960002986 dinoprostone Drugs 0.000 description 2
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000012642 immune effector Substances 0.000 description 2
- 230000008073 immune recognition Effects 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000017307 interleukin-4 production Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000008823 permeabilization Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000006433 tumor necrosis factor production Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
- 102100034278 Annexin A6 Human genes 0.000 description 1
- 108090000656 Annexin A6 Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- -1 CD86 Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 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 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 208000003164 Diplopia Diseases 0.000 description 1
- 102100023431 E3 ubiquitin-protein ligase TRIM21 Human genes 0.000 description 1
- 101710164941 E3 ubiquitin-protein ligase TRIM21 Proteins 0.000 description 1
- 238000011891 EIA kit Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102100029966 HLA class II histocompatibility antigen, DP alpha 1 chain Human genes 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 description 1
- 101000981050 Homo sapiens Ceramide glucosyltransferase Proteins 0.000 description 1
- 101000864089 Homo sapiens HLA class II histocompatibility antigen, DP alpha 1 chain Proteins 0.000 description 1
- 101000930802 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 1 chain Proteins 0.000 description 1
- 101000968032 Homo sapiens HLA class II histocompatibility antigen, DR beta 3 chain Proteins 0.000 description 1
- 101000972485 Homo sapiens Lupus La protein Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101500025624 Homo sapiens Transforming growth factor beta-2 Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100022742 Lupus La protein Human genes 0.000 description 1
- 101710175243 Major antigen Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 108010051791 Nuclear Antigens Proteins 0.000 description 1
- 102000019040 Nuclear Antigens Human genes 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108010083312 T-Cell Antigen Receptor-CD3 Complex Proteins 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 206010052779 Transplant rejections Diseases 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
- 108091026838 U1 spliceosomal RNA Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 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
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 229940045644 human calcitonin Drugs 0.000 description 1
- 230000008938 immune dysregulation Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 1
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000022023 interleukin-5 production Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 208000018731 motor weakness Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108010086662 phytohemagglutinin-M Proteins 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/13—Tumour cells, irrespective of tissue of origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4614—Monocytes; Macrophages
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/936,537 US6884413B1 (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (GCS) |
CA002367132A CA2367132A1 (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (gcs) |
AU40295/00A AU772142B2 (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (GCS) |
EP00919639A EP1165101A2 (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (gcs) |
JP2000606260A JP2002539271A (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific non-responsiveness by glioblastoma culture supernatant (GCS) |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12599699P | 1999-03-24 | 1999-03-24 | |
US60/125,996 | 1999-03-24 |
Publications (3)
Publication Number | Publication Date |
---|---|
WO2000056356A2 true WO2000056356A2 (en) | 2000-09-28 |
WO2000056356A3 WO2000056356A3 (en) | 2001-01-25 |
WO2000056356B1 WO2000056356B1 (en) | 2001-08-16 |
Family
ID=22422453
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/007959 WO2000056356A2 (en) | 1999-03-24 | 2000-03-23 | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (gcs) |
Country Status (6)
Country | Link |
---|---|
US (1) | US6884413B1 (en) |
EP (1) | EP1165101A2 (en) |
JP (1) | JP2002539271A (en) |
AU (1) | AU772142B2 (en) |
CA (1) | CA2367132A1 (en) |
WO (1) | WO2000056356A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2293667A2 (en) * | 2008-05-27 | 2011-03-16 | Kyowa Hakko Kirin Co., Ltd. | Interleukin 10 receptor (il-10r) antibodies and methods of use |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050084967A1 (en) | 2002-06-28 | 2005-04-21 | Xcyte Therapies, Inc. | Compositions and methods for eliminating undesired subpopulations of T cells in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0155433A1 (en) * | 1984-03-23 | 1985-09-25 | Adriano Fontana | Immunosuppressant factor |
EP0159289A1 (en) * | 1984-03-23 | 1985-10-23 | Sandoz Ag | Immunosuppressant factor |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4728614A (en) | 1983-05-18 | 1988-03-01 | Ortho Pharmaceutical | Mutant human T cell line producing immunosuppressive factor and method for obtaining such mutants |
US5095095A (en) | 1984-03-23 | 1992-03-10 | Sandoz Ltd. | Immunosuppressant factor protein capable of inhibiting T-cell mechanisms |
US5468481A (en) | 1988-06-23 | 1995-11-21 | Amergen, Inc. | MHC class II-peptide conjugates useful in ameliorating autoimmunity |
EP0815204B1 (en) | 1995-03-17 | 2006-09-06 | The Regents Of The University Of California | Method for treating tumors by alloactivated human donor lymphocytes |
US5871728A (en) | 1995-03-31 | 1999-02-16 | University Of Pittsburgh | Method of regulating dendritic cell maturation |
-
2000
- 2000-03-23 JP JP2000606260A patent/JP2002539271A/en active Pending
- 2000-03-23 US US09/936,537 patent/US6884413B1/en not_active Expired - Fee Related
- 2000-03-23 AU AU40295/00A patent/AU772142B2/en not_active Ceased
- 2000-03-23 WO PCT/US2000/007959 patent/WO2000056356A2/en not_active Application Discontinuation
- 2000-03-23 CA CA002367132A patent/CA2367132A1/en not_active Abandoned
- 2000-03-23 EP EP00919639A patent/EP1165101A2/en not_active Withdrawn
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0155433A1 (en) * | 1984-03-23 | 1985-09-25 | Adriano Fontana | Immunosuppressant factor |
EP0159289A1 (en) * | 1984-03-23 | 1985-10-23 | Sandoz Ag | Immunosuppressant factor |
Non-Patent Citations (2)
Title |
---|
JIANG-PING ZOU ET AL.: "Human Glioma-Induced Immunosuppression Involves Soluble Factor(s) That Alters Monocyte Cytokine Profile and Surface Markers" JOURNAL OF IMMUNOLOGY., vol. 162, 1999, pages 4882-4892, XP002149737 THE WILLIAMS AND WILKINS CO. BALTIMORE., US ISSN: 0022-1767 * |
LORRI A. MORFORD ET AL. : "Apoptotic elimination of peripheral T lymphocytes in patients with primary intracranial tumors" JOURNAL OF NEUROSURGERY., vol. 91, no. 6, December 1999 (1999-12), pages 935-946, XP000952674 XX, XX ISSN: 0022-3085 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2293667A2 (en) * | 2008-05-27 | 2011-03-16 | Kyowa Hakko Kirin Co., Ltd. | Interleukin 10 receptor (il-10r) antibodies and methods of use |
EP2293667A4 (en) * | 2008-05-27 | 2012-07-18 | Kyowa Hakko Kirin Co Ltd | Interleukin 10 receptor (il-10r) antibodies and methods of use |
US8420784B2 (en) | 2008-05-27 | 2013-04-16 | Kyowa Hakko Kirin Co., Ltd. | Interleukin 10 receptor, (IL-10R) antibodies |
Also Published As
Publication number | Publication date |
---|---|
AU772142B2 (en) | 2004-04-08 |
WO2000056356A3 (en) | 2001-01-25 |
WO2000056356B1 (en) | 2001-08-16 |
US6884413B1 (en) | 2005-04-26 |
JP2002539271A (en) | 2002-11-19 |
AU4029500A (en) | 2000-10-09 |
EP1165101A2 (en) | 2002-01-02 |
CA2367132A1 (en) | 2000-09-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Quah et al. | The immunogenicity of dendritic cell-derived exosomes | |
Giganti et al. | Treg cell therapy: How cell heterogeneity can make the difference | |
JPH07505527A (en) | In vitro development of human dendritic cells and their uses | |
JP2004529631A (en) | CD4 + CD25 + regulatory T cells from human blood | |
US10881692B2 (en) | Compositions for establishing mixed chimerism and methods of manufacture thereof | |
Li et al. | Exosomes released from human bone marrow–derived mesenchymal stem cell attenuate acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in mice | |
US20230357718A1 (en) | Methods and materials for expanding antigen-specific t cells in culture | |
US20100092499A1 (en) | Alpha Thymosin Peptides as Cancer Vaccine Adjuvants | |
JP2019537562A (en) | Immunogenic arginase peptide | |
Koga et al. | IL10-and IL35-secreting MutuDC lines act in cooperation to inhibit memory T cell activation through LAG-3 expression | |
Tambuyzer et al. | Allogeneic stromal cell implantation in brain tissue leads to robust microglial activation | |
US20150004182A1 (en) | Population of immunoregulatory t cells specific for an irrelevant antigen and uses thereof for preventing or treating immune diseases | |
AU772142B2 (en) | Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (GCS) | |
WO2010129770A1 (en) | Methods for expanding human t regulatory cells and uses of same | |
US9211326B2 (en) | Method of enhancing the proliferative phase of a primary T cell response | |
RU2678569C1 (en) | Method of pressing the tumors metastasis | |
EP2393505B1 (en) | Use of specific peptides in the preparation of a medicament for the treatment of monoclonal gammopathy of undetermined significance (mgus) or of smoldering multiple myeloma (smm) | |
CN1213143C (en) | Method and compositions for improving allogeneic hematopoietic cell transplantation | |
Wei | Targeting dendritic cell metabolism to induce immune tolerance | |
Huang et al. | Cell therapies and its derivatives as immunomodulators in vascularized composite allotransplantation | |
WO2022253957A1 (en) | Person-tailored t cell composition targeting merkel cell carcinoma | |
KR100797049B1 (en) | Cd4 t cells having therapeutic effects on atopic dermatitis | |
KR20030085659A (en) | Therapeutic cancer exosome and cancer vaccine using itself | |
Vogtenhuber | Signaling pathways in regulatory T cells | |
Semple | Generation and Application of Antigen-Specific Induced Regulatory T cells in Allogeneic Bone Marrow Transplantation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
AK | Designated states |
Kind code of ref document: B1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: B1 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
B | Later publication of amended claims | ||
ENP | Entry into the national phase |
Ref document number: 2367132 Country of ref document: CA Ref country code: CA Ref document number: 2367132 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09936537 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 606260 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000919639 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2000919639 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000919639 Country of ref document: EP |