RU2018124640A - Фармацевтическая композиция для предотвращения или лечения заболеваний, опосредованных регуляторными т-клетками - Google Patents
Фармацевтическая композиция для предотвращения или лечения заболеваний, опосредованных регуляторными т-клетками Download PDFInfo
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- 239000008194 pharmaceutical composition Substances 0.000 title claims 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims 7
- 201000010099 disease Diseases 0.000 title claims 6
- 210000003289 regulatory T cell Anatomy 0.000 title claims 6
- 230000001404 mediated effect Effects 0.000 title claims 4
- 230000002265 prevention Effects 0.000 title 1
- 210000001744 T-lymphocyte Anatomy 0.000 claims 8
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims 8
- 206010016654 Fibrosis Diseases 0.000 claims 6
- 239000002158 endotoxin Substances 0.000 claims 6
- 230000004761 fibrosis Effects 0.000 claims 6
- 229920006008 lipopolysaccharide Polymers 0.000 claims 6
- 238000000034 method Methods 0.000 claims 5
- 239000003446 ligand Substances 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 210000000130 stem cell Anatomy 0.000 claims 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 3
- 108010002352 Interleukin-1 Proteins 0.000 claims 3
- 108010002350 Interleukin-2 Proteins 0.000 claims 3
- 108090001005 Interleukin-6 Proteins 0.000 claims 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 3
- 239000000126 substance Substances 0.000 claims 3
- 201000004384 Alopecia Diseases 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000009137 Behcet syndrome Diseases 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 2
- 206010020880 Hypertrophy Diseases 0.000 claims 2
- 102000053646 Inducible T-Cell Co-Stimulator Human genes 0.000 claims 2
- 108700013161 Inducible T-Cell Co-Stimulator Proteins 0.000 claims 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 2
- 108091007960 PI3Ks Proteins 0.000 claims 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 2
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 2
- 231100000360 alopecia Toxicity 0.000 claims 2
- 208000007502 anemia Diseases 0.000 claims 2
- 208000002399 aphthous stomatitis Diseases 0.000 claims 2
- 201000001981 dermatomyositis Diseases 0.000 claims 2
- 230000004069 differentiation Effects 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 201000010260 leiomyoma Diseases 0.000 claims 2
- 230000035755 proliferation Effects 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 1
- 208000033116 Asbestos intoxication Diseases 0.000 claims 1
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 208000001640 Fibromyalgia Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 241000721454 Pemphigus Species 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010065159 Polychondritis Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 206010039710 Scleroderma Diseases 0.000 claims 1
- 201000010001 Silicosis Diseases 0.000 claims 1
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 1
- 206010042953 Systemic sclerosis Diseases 0.000 claims 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 1
- 206010043781 Thyroiditis chronic Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 208000010638 acquired aplastic anemia Diseases 0.000 claims 1
- 206010003441 asbestosis Diseases 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 230000001363 autoimmune Effects 0.000 claims 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 201000002491 encephalomyelitis Diseases 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 230000001969 hypertrophic effect Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
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- 206010025135 lupus erythematosus Diseases 0.000 claims 1
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- 206010028417 myasthenia gravis Diseases 0.000 claims 1
- 201000006292 polyarteritis nodosa Diseases 0.000 claims 1
- 208000005987 polymyositis Diseases 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 210000001685 thyroid gland Anatomy 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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Claims (18)
1. Фармацевтическая композиция для предотвращения или лечения заболевания, опосредованного регуляторными Т-клетками, причем указанная фармацевтическая композиция содержит лиганд индуцированного Т-клеточного костимулятора (ICOSL) или мезенхимальную стволовую клетку, гиперэкспрессирующую ICOSL.
2. Фармацевтическая композиция по п. 1, в которой указанный ICOSL получен из мезенхимальной стволовой клетки.
3. Фармацевтическая композиция по п. 1, в которой указанный ICOSL экспрессируется на поверхности мезенхимальной стволовой клетки.
4. Фармацевтическая композиция по п. 1, в которой указанная стволовая клетка представляет собой клональную стволовую клетку.
5. Фармацевтическая композиция по п. 1, в которой указанная стволовая клетка представляет собой мезенхимальную стволовую клетку, полученную из костного мозга.
6. Фармацевтическая композиция по п. 1, в которой указанный ICOSL повышает экспрессию индуцируемого Т-клеточного костимулятора (ICOS) Т-клетки.
7. Фармацевтическая композиция по п. 1, в которой указанный ICOSL активирует путь передачи сигнала PI3K (фосфоинозитид-3-киназы)-Akt.
8. Фармацевтическая композиция по п. 1, в которой указанная мезенхимальная стволовая клетка обработана одним или более веществом, выбранным из группы, состоящей из IL-1β, ФНО-α, IL-6, IL-2, IL-1 и LPS (липополисахарида).
9. Фармацевтическая композиция по п. 1, где указанное заболевание, опосредованное регуляторными Т-клетками, представляет собой воспалительное заболевание или аутоиммунное заболевание.
10. Фармацевтическая композиция по п. 9, где указанное воспалительное заболевание включает одно или более заболевание, выбранное из группы, состоящей из волчанки, синдрома Шегрена, ревматоидного артрита, фибромиозита, склеродермии, анкилозирующего спондилита, болезни Бехчета, афтозного стоматита, синдрома Гийена Барре, очаговой алопеции, дерматомиозита, болезни Крона, колита, узелкового полиартериита, рецидивирующего полихондрита и аутоиммунной тромбоцитопении.
11. Фармацевтическая композиция по п. 9, где указанное аутоиммунное заболевание включает одно или более заболевание, выбранное из группы, состоящей из ревматоидного артрита, системной склеродермии, инсулинзависимого сахарного диабета у детей вследствие разрушения клеток поджелудочной железы, очаговой алопеции, псориаза, пемфигуса, астмы, афтозного стоматита, хронического тиреоидита, частично приобретенной апластической анемии, первичного гепатоцирроза, язвенного колита, болезни Бехчета, болезни Крона, силикоза, асбестоза, болезни почек IgA-типа, пострептококкового гломерулонефрита, синдрома Шегрена, синдрома Гийена Барре, дерматомиозита, полимиозита, рассеянного склероза, аутоиммунной гемолитической анемии, аутоиммунного энцефаломиелита, миастении гравис, гиперплазии щитовидной железы Грейвса, узелкового полиартериита, анкилозирующего спондилоартрита, фиброзита, височного артериита, болезни Вильсона, синдрома Пакони, множественной миеломы и системной красной волчанки.
12. Композиция для индуцирования дифференцировки и пролиферации CD4+ Т-клетки в регуляторную Т-клетку, причем указанная композиция содержит лиганд индуцированного Т-клеточного костимулятора (ICOSL) или мезенхимальную стволовую клетку, гиперэкспрессирующую ICOSL.
13. Композиция по п. 12, где указанная композиция содержит одно или более вещество, выбранное из группы, состоящей из IL-1β, ФНО-α, IL-6, IL-2, IL-1 и ЛПС (липополисахарида).
14. Способ индуцирования дифференцировки и пролиферации CD4+ Т-клетки в регуляторную Т-клетку, причем указанный способ включает:
обработку CD4+ Т-клетки in vitro лигандом индуцированного Т-клеточного костимулятора (ICOSL) или мезенхимальной стволовой клеткой, гиперэкспрессирующей ICOSL.
15. Способ по п. 14, отличающийся тем, что указанные стволовые клетки с повышенной экспрессией ICOSL предварительно обработаны одним или более веществом, выбранным из группы, состоящей IL-1β, ФНО-α, IL-6, IL-2, IL-1 и ЛПС (липополисахарида).
16. Способ предотвращения или лечения заболевания, опосредованного регуляторными Т-клетками, причем указанный способ включает:
введение индивидууму лиганда индуцированного Т-клеточного костимулятора (ICOSL) или мезенхимальной стволовой клетки, гиперэкспрессирующей ICOSL.
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