EP1463799A2 - Procedes d'induction de lymphocytes t regulateurs professionnels et des lymphocytes t produisant des cytokines - Google Patents
Procedes d'induction de lymphocytes t regulateurs professionnels et des lymphocytes t produisant des cytokinesInfo
- Publication number
- EP1463799A2 EP1463799A2 EP02799306A EP02799306A EP1463799A2 EP 1463799 A2 EP1463799 A2 EP 1463799A2 EP 02799306 A EP02799306 A EP 02799306A EP 02799306 A EP02799306 A EP 02799306A EP 1463799 A2 EP1463799 A2 EP 1463799A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- cells
- regulatory
- cell
- population
- tgf
- 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.)
- Withdrawn
Links
- 102000004127 Cytokines Human genes 0.000 title claims abstract description 59
- 108090000695 Cytokines Proteins 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 51
- 230000001105 regulatory effect Effects 0.000 title claims description 85
- 230000006698 induction Effects 0.000 title abstract description 8
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 124
- 230000000694 effects Effects 0.000 claims abstract description 117
- 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 96
- 210000004027 cell Anatomy 0.000 claims description 244
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 82
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 82
- 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 claims description 81
- 239000000203 mixture Substances 0.000 claims description 66
- 108010002350 Interleukin-2 Proteins 0.000 claims description 43
- 102000000588 Interleukin-2 Human genes 0.000 claims description 43
- 229940126530 T cell activator Drugs 0.000 claims description 23
- 230000028993 immune response Effects 0.000 claims description 22
- 239000000427 antigen Substances 0.000 claims description 20
- 102000036639 antigens Human genes 0.000 claims description 20
- 108091007433 antigens Proteins 0.000 claims description 20
- 102000003812 Interleukin-15 Human genes 0.000 claims description 17
- 108090000172 Interleukin-15 Proteins 0.000 claims description 17
- 230000001594 aberrant effect Effects 0.000 claims description 7
- 210000001616 monocyte Anatomy 0.000 claims description 7
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 4
- 108010084313 CD58 Antigens Proteins 0.000 claims description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 4
- 210000004443 dendritic cell Anatomy 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 claims description 3
- 102000007079 Peptide Fragments Human genes 0.000 claims description 3
- 108010033276 Peptide Fragments Proteins 0.000 claims description 3
- 230000000961 alloantigen Effects 0.000 claims description 3
- 241000191940 Staphylococcus Species 0.000 claims description 2
- 210000002540 macrophage Anatomy 0.000 claims description 2
- 230000001747 exhibiting effect Effects 0.000 claims 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 85
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 85
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 85
- 238000011282 treatment Methods 0.000 description 26
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 21
- 208000023275 Autoimmune disease Diseases 0.000 description 19
- 230000001404 mediated effect Effects 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 17
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 14
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000012636 effector Substances 0.000 description 11
- 210000000987 immune system Anatomy 0.000 description 11
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 10
- 239000012190 activator Substances 0.000 description 10
- 239000011324 bead Substances 0.000 description 10
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 9
- 230000000735 allogeneic effect Effects 0.000 description 9
- 230000003092 anti-cytokine Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 238000001994 activation Methods 0.000 description 8
- 239000000306 component Substances 0.000 description 8
- 230000003472 neutralizing effect Effects 0.000 description 8
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 8
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 7
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 7
- 229940045513 CTLA4 antagonist Drugs 0.000 description 7
- 108091008874 T cell receptors Proteins 0.000 description 7
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 210000003563 lymphoid tissue Anatomy 0.000 description 7
- 239000003226 mitogen Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 208000009329 Graft vs Host Disease Diseases 0.000 description 6
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 6
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 6
- 102100033467 L-selectin Human genes 0.000 description 6
- 206010052779 Transplant rejections Diseases 0.000 description 6
- 208000024908 graft versus host disease Diseases 0.000 description 6
- 230000001771 impaired effect Effects 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 102000003814 Interleukin-10 Human genes 0.000 description 5
- 108090000174 Interleukin-10 Proteins 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102100025390 Integrin beta-2 Human genes 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108010092694 L-Selectin Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 3
- 208000037908 antibody-mediated disorder Diseases 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- -1 autoantibodies Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 208000037816 tissue injury Diseases 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000003807 Graves Disease Diseases 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 208000001204 Hashimoto Disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101000935040 Homo sapiens Integrin beta-2 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
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 201000011152 Pemphigus Diseases 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 108010057085 cytokine receptors Proteins 0.000 description 2
- 102000003675 cytokine receptors Human genes 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 208000007475 hemolytic anemia Diseases 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 210000005210 lymphoid organ Anatomy 0.000 description 2
- 230000007193 modulation by symbiont of host erythrocyte aggregation Effects 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 231100000065 noncytotoxic Toxicity 0.000 description 2
- 230000002020 noncytotoxic effect Effects 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OQPDPIPLWCUACY-UHFFFAOYSA-N 2-aminoethylthiourea;hydrobromide Chemical compound [Br-].NCC[NH+]=C(N)S OQPDPIPLWCUACY-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 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
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 238000003794 Gram staining Methods 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 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 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 102000016551 L-selectin Human genes 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003172 anti-dna Effects 0.000 description 1
- 230000000947 anti-immunosuppressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010370 cell cloning Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000459 effect on growth Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940027278 hetastarch Drugs 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 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
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000007896 negative regulation of T cell activation Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000001986 peyer's patch Anatomy 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010919 regulation of germinal center formation Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 229940043517 specific immunoglobulins Drugs 0.000 description 1
- 238000013190 sterility testing Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/15—Transforming growth factor beta (TGF-β)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
Definitions
- the present inventions provides methods for inhibiting aberrant or undesirable immune responses comprising administering the regulatory T cells generated using the regulatory compositions described herein.
- activated professional regulatory T cells When activated professional regulatory T cells are mixed with conventional T cells, they generate a population of cytokine producing regulatory T cells when treated with a T cell activation ( Figure 1 B). Significantly, repeated treatment with a regulatory composition comprising cytokines is not needed to generate this population of cytokine producing regulatory T cells.
- the memory-effector subset which contains the vast majority of cells capable of responding to recall antigens and can be generated in vitro from the aforementioned na ⁇ ve subset following appropriate activation, predominantly expresses the low molecular weight, high activity, RO CD45 isoform and shows efficient effector function (e.g., production of effector cytokines, cytotoxicity), increased CD95/FAS expression, and increased susceptibility to apoptosis, high levels of CD11a/CD18 and the other general adhesion molecules listed above, and heterogenous expression of the L-selectin, ⁇ 4 ⁇ 7 integrin, and CD27 (Picker and Siegelman, (1999) "Lymphoid Tissues and Organs" in W.
- T cells are prepared by immediate rosetting with 2-aminoethylisothiouronium bromide-treated SRBC. T cells are further purified from rosetting cells by staining with antibodies (Abs) to CD16, CD74, and CD11b and deleting reactive cells using immunomagnetic beads. The percentage of CD3+ cells in this fraction is usually greater than 96% (see Zheng, et al., (2002) J. Immunol., 169: 4183-4189).
- the kit further comprises at least one dose of an regulatory composition.
- Dose in this context means an amount of the regulatory composition such as cytokines, that is sufficient to cause an effect. In some cases, multiple doses may be included.
- the dose may be added to the cell treatment container using a port; alternatively, in a preferred embodiment, the dose is already present in the cell treatment container.
- the dose is in a lyophilized form for stability, that can be reconstituted using the cell media, or other reagents.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Neurology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Physical Education & Sports Medicine (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
Abstract
Cette invention porte, de manière générale, sur des procédés utilisés dans l'induction des lymphocytes T ayant une activité suppressive. Ces procédés sont plus particulièrement utilisés pour générer des lymphocytes T régulateurs professionnels et des lymphocytes T produisant des cytokines et dont l'activité suppressive est améliorée.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34265501P | 2001-12-21 | 2001-12-21 | |
| US342655P | 2001-12-21 | ||
| US37410202P | 2002-04-19 | 2002-04-19 | |
| US374102P | 2002-04-19 | ||
| PCT/US2002/041288 WO2003059264A2 (fr) | 2001-12-21 | 2002-12-20 | Procedes d'induction de lymphocytes t regulateurs professionnels et des lymphocytes t produisant des cytokines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1463799A2 true EP1463799A2 (fr) | 2004-10-06 |
| EP1463799A4 EP1463799A4 (fr) | 2006-01-18 |
Family
ID=26993124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02799306A Withdrawn EP1463799A4 (fr) | 2001-12-21 | 2002-12-20 | Procedes d'induction de lymphocytes t regulateurs professionnels et des lymphocytes t produisant des cytokines |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1463799A4 (fr) |
| JP (1) | JP2005514054A (fr) |
| AU (1) | AU2002364230B2 (fr) |
| CA (1) | CA2469800A1 (fr) |
| WO (1) | WO2003059264A2 (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1715034A4 (fr) * | 2004-02-12 | 2007-11-21 | Immunofrontier Inc | Cellulle r gulatrice controllant l' activite immunologique d' une cellule thymodependante |
| EP1812563B1 (fr) | 2004-10-29 | 2013-04-10 | Benaroya Research Institute at Virginia Mason | Méthodes de génération de cellules t de régulation cd4+cd25+ spécifiques à un antigène, compositions et méthodes d'utilisation associées |
| US8852581B2 (en) * | 2005-08-31 | 2014-10-07 | Ith Immune Therapy Holdings Ab | Treatment of inflammatory bowel disease |
| ITRM20070437A1 (it) * | 2007-08-10 | 2009-02-11 | Istituto Naz Per Le Malattie I | Metodo per la generazione ed espansione di cellule t gamma/delta regolatorie cellule cosi' ottenute e loro impieghi |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001077299A2 (fr) * | 2000-04-11 | 2001-10-18 | University Of Southern California | Methode de prevention de rejet de greffe par utilisation de tgf-$g(b) pour induire des cellules t suppresseurs |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5374549A (en) * | 1991-01-31 | 1994-12-20 | Terumo Corporation | Process of enriching adherent CD4+ T cells from monocyte depleted peripheral blood mononuclear cells with interleukin 2 and interleukin 4 |
| PT1028738E (pt) * | 1997-11-05 | 2003-08-29 | Univ Southern California | Utilizacao de citoquinas e mitogenios para inibir respostas imunitarias patologicas |
| ATE332963T1 (de) * | 1999-01-22 | 2006-08-15 | Schepens Eye Res Inst | Aktivierung von regulatorischen t zellen durch ein alpha-melanocyten stimulierendes hormon |
| US6746670B2 (en) * | 2000-08-15 | 2004-06-08 | Schering Corporation | Regulatory T cells; methods |
| EP1241249A1 (fr) * | 2001-03-12 | 2002-09-18 | Gerold Schuler | Lymphocytes T CD4+CD25+ régulateurs provenant du sang humain |
| FR2824567B1 (fr) * | 2001-05-11 | 2003-08-08 | Inst Nat Sante Rech Med | Procede d'obtention de lymphocytes tr1 regulateurs specifiques d'antigene |
-
2002
- 2002-12-20 AU AU2002364230A patent/AU2002364230B2/en not_active Ceased
- 2002-12-20 CA CA002469800A patent/CA2469800A1/fr not_active Abandoned
- 2002-12-20 WO PCT/US2002/041288 patent/WO2003059264A2/fr active Application Filing
- 2002-12-20 EP EP02799306A patent/EP1463799A4/fr not_active Withdrawn
- 2002-12-20 JP JP2003559429A patent/JP2005514054A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001077299A2 (fr) * | 2000-04-11 | 2001-10-18 | University Of Southern California | Methode de prevention de rejet de greffe par utilisation de tgf-$g(b) pour induire des cellules t suppresseurs |
Non-Patent Citations (4)
| Title |
|---|
| HORWITZ D A ET AL: "Role of NK cells and TGF-beta in the regulation of T-cell-dependent antibody production in health and autoimmune disease." MICROBES AND INFECTION / INSTITUT PASTEUR. DEC 1999, vol. 1, no. 15, December 1999 (1999-12), pages 1305-1311, XP002355571 ISSN: 1286-4579 * |
| See also references of WO03059264A2 * |
| STEPHENS L A ET AL: "Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro." EUROPEAN JOURNAL OF IMMUNOLOGY. APR 2001, vol. 31, no. 4, April 2001 (2001-04), pages 1247-1254, XP002210570 ISSN: 0014-2980 * |
| ZHENG SONG GUO ET AL: "Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors." JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 15 OCT 2002, vol. 169, no. 8, 15 October 2002 (2002-10-15), pages 4183-4189, XP002355572 ISSN: 0022-1767 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1463799A4 (fr) | 2006-01-18 |
| CA2469800A1 (fr) | 2003-07-24 |
| AU2002364230A1 (en) | 2003-07-30 |
| WO2003059264A3 (fr) | 2004-02-12 |
| AU2002364230B2 (en) | 2008-05-01 |
| WO2003059264A9 (fr) | 2004-11-11 |
| WO2003059264A2 (fr) | 2003-07-24 |
| JP2005514054A (ja) | 2005-05-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20060067912A1 (en) | Methods for the induction of professional and cytokine-producing regulatory T cells | |
| JP5008810B2 (ja) | 抑制性Ｔ細胞を誘導するためにＴＧＦ−βを用いる移植拒絶反応を防止する方法 | |
| US20060286067A1 (en) | Methods for making and using regulatory T cells | |
| US20080175823A1 (en) | Use of Cytokines and Mitogens to Inhibit Pathological Immune Responses | |
| CA2552891A1 (fr) | Lymphocytes t regulateurs supprimant l'auto-immunite | |
| AU2001253400A1 (en) | A method to prevent graft rejection using TGF-beta to induce T suppressor cells | |
| US6803036B1 (en) | Use of cytokines, cells and mitogens to inhibit graft versus host disease | |
| JP4256431B2 (ja) | 移植片−対−宿主疾患を抑制するサイトカイン、細胞およびマイトジェンの使用 | |
| AU1382799A (en) | Use of cytokines and mitogens to inhibit pathological immune responses | |
| EP1173549B1 (fr) | Utilisation de cytokines et de mitogenes pour empecher des reponses immunitaires pathologiques | |
| AU2002364230B2 (en) | Methods for the induction of professional and cytokine-producing regulatory cells | |
| Watanabe et al. | Transforming growth factor-β/interleukin-2–induced regulatory CD4+ T cells prolong cardiac allograft survival in rats | |
| AU2007202534B2 (en) | A method to prevent graft rejection using TGF-beta to induce T suppressor cells | |
| AU2011218736A1 (en) | A method to prevent graft rejection using TGF-beta to induce T suppressor cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20040709 |
|
| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SI SK TR |
|
| AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO |
|
| A4 | Supplementary search report drawn up and despatched |
Effective date: 20051205 |
|
| 17Q | First examination report despatched |
Effective date: 20071119 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20100803 |