RU2020130838A - Универсальные антигенпрезентирующие клетки и их применения - Google Patents
Универсальные антигенпрезентирующие клетки и их применения Download PDFInfo
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- RU2020130838A RU2020130838A RU2020130838A RU2020130838A RU2020130838A RU 2020130838 A RU2020130838 A RU 2020130838A RU 2020130838 A RU2020130838 A RU 2020130838A RU 2020130838 A RU2020130838 A RU 2020130838A RU 2020130838 A RU2020130838 A RU 2020130838A
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- immunocytes
- uapc
- cells
- leukemia
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- 210000000612 antigen-presenting cell Anatomy 0.000 title claims 2
- 238000000034 method Methods 0.000 claims 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 8
- 210000004700 fetal blood Anatomy 0.000 claims 8
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 7
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- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 1
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Claims (61)
1. Универсальная антигенпрезентирующая клетка (UAPC), модифицированная для экспрессии (1) CD48 и/или CS1 (CD319), (2) связанного с мембраной интерлейкина-21 (mbIL-21) и (3) лиганда 41BB (41BBL).
2. UAPC по п.1, экспрессирующая CD48.
3. UAPC по п.1, экспрессирующая CS1.
4. UAPC по п.1, экспрессирующая CD48 и CS1.
5. UAPC по п.1, по существу не имеющая экспрессии эндогенных молекул HLA класса I, II или CDId.
6. UAPC по п.1, экспрессирующая ICAM-1 (CD54) и LFA-3 (CD58).
7. UAPC по п.1, где UAPC представляет собой происходящую из клетки лейкоза UAPC.
8. UAPC по п.7, где происходящую из клетки лейкоза UAPC дополнительно определяют как клетку K562.
9. UAPC по п.1, модифицированная посредством ретровирусной трансдукции.
10. UAPC по п.9, где ретровирусную трансдукцию дополнительно определяют как трансдукцию вирусной конструкцией из SEQ ID NO: 1 и/или SEQ ID N0:2.
11. UAPC по любому из пп. 1-10, являющаяся облученной.
12. Способ размножения иммуноцитов, включающий культивирование иммуноцитов в присутствии эффективного количества UAPC по любому из пп. 1-11.
13. Способ по п.12, где иммуноциты и UAPC культивируют в соотношении от 3:1 до 1:3.
14. Способ по п.12, где иммуноциты и UAPC культивируют в соотношении 1:2.
15. Способ по п.12, где размножение проводят в присутствии IL-2.
16. Способ по п.15, где IL-2 присутствует в концентрации 10-500 ед./мл.
17. Способ по п.15, где IL-2 присутствует в концентрации 100-300 ед./мл.
18. Способ по п.15, где IL-2 присутствует в концентрации 200 ед./мл.
19. Способ по п.15, где IL-2 представляет собой рекомбинантный человеческий IL-2.
20. Способ по п.15, где IL-2 восполняют каждые 2-3 суток.
21. Способ по п.12, где UAPC добавляют по меньшей мере второй раз.
22. Способ по п.12, где иммуноциты представляют собой клетки NK или T-клетки.
23. Способ по п.12, где иммуноциты представляют собой клетки NK.
24. Способ по п.12, где иммуноциты представляют собой T-клетки.
25. Способ по п.12, где иммуноциты происходят из пуповинной крови (CB), периферической крови (PB), стволовых клеток или костного мозга.
26. Способ по п.12, где стволовые клетки представляют собой индуцированные плюрипотентные стволовые клетки.
27. Способ по п.12, где иммуноциты получены из CB.
28. Способ по п.27, где CB пулирована из 2 или более индивидуальных доз пуповинной крови.
29. Способ по п.27, где CB пулирована из 3, 4, 5, 6, 7 или 8 индивидуальных доз пуповинной крови.
30. Способ по п.23, где клетки NK представляют собой мононуклеарные клетки CB (CBMC).
31. Способ по п.23, где клетки NK дополнительно определяют как CD56+ клетки NK.
32. Способ по п.12, где способ осуществляют в бессыровоточной среде.
33. Способ по любому из пп. 12-32, где иммуноциты модифицируют для экспрессии химерного рецептора антигена (CAR).
34. Способ по п.33, где CAR содержит гуманизированный антигенсвязывающий домен.
35. Способ по п.33, где CAR содержит антигенсвязывающий домен для CD19, CD123, мезотелина, CD5, CD47, CLL-1, CD33, CD99, U5snRNP200, CD200, CS1, BAFF-R, ROR-1 или BCMA.
36. Способ по п.33, где CAR содержит антигенсвязывающий домен для CD19 или CD123.
37. Способ по п.33, где CAR содержит IL-15.
38. Способ по п.33, где CAR содержит ген самоубийства.
39. Способ по п.38, где ген самоубийства представляет собой CD20, CD52, EGFRv3 или индуцируемую каспазу 9.
40. Популяция размноженных иммуноцитов, полученная в соответствии со способами по любому из пп. 12-39.
41. Фармацевтическая композиция, содержащая популяцию размноженных иммуноцитов по п.40 и фармацевтически приемлемый носитель.
42. Композиция, содержащая эффективное количество размноженных иммуноцитов по п.40 для применения в лечении заболевания или нарушения у субъекта.
43. Способ лечения заболевания или нарушения у субъекта, включающий введение терапевтически эффективного количества размноженных иммуноцитов по п.40 субъекту.
44. Способ по п.43, где заболевание или нарушение представляет собой злокачественную опухоль, воспаление, реакцию трансплантат против хозяина, отторжение трансплантата, аутоиммунное нарушение, иммунодефицитное заболевание, В-клеточное злокачественное новообразование или инфекцию.
45. Способ по п.44, где злокачественная опухоль представляет собой лейкоз.
46. Способ по п.45, где лейкоз представляет собой острый лимфобластный лейкоз (ALL), хронический лимфоцитарный лейкоз (CLL), острый миелогенный лейкоз (AML) или хронический миелогенный лейкоз (CML).
47. Способ по п.43, где иммуноциты являются аллогенными.
48. Способ по п.43, где иммуноциты являются аутологичными.
49. Способ по п.43, где иммуноциты представляют собой клетки NK или T-клетки.
50. Способ по п.43, где иммуноциты представляют собой клетки NK.
51. Способ по п.43, где нарушение представляет собой реакцию трансплантат против хозяина (GVHD).
52. Способ по п.43, где нарушение представляет собой рассеянный склероз, воспалительное заболевание кишечника, ревматоидный артрит, диабет типа I, системную красную волчанку, контактную гиперчувствительность, астму или синдром Шегрена.
53. Способ по п.43, где субъект представляет собой человека.
54. Способ по п.43, дополнительно включающий введение по меньшей мере второго лекарственного средства.
55. Способ по п.54, где по меньшей мере второе лекарственное средство представляет собой терапевтически эффективное количество противоракового средства, иммуномодулирующего средства или иммуносупрессивного средства.
56. Способ по п.55, где противораковое средство представляет собой химиотерапию, радиотерапию, генотерапию, хирургию, гормонотерапию, антиангиогенную терапию или иммунотерапию.
57. Способ по п.55, где иммуносупрессивное средство представляет собой ингибитор кальциневрина, ингибитор mTOR, антитело, химиотерапевтическое средство, облучение, хемокин, интерлейкины или ингибитор хемокина или интерлейкина.
58. Способ по п.54, где иммуноциты и/или по меньшей мере второе лекарственное средство вводят внутривенно, внутрибрюшинно, интратрахеально, внутрь опухоли, внутримышечно, эндоскопически, внутрь очага, чрескожно, подкожно, местно, или посредством прямой инъекции или перфузии.
59. Способ по п.54, где второе лекарственное средство представляет собой антитело.
60. Способ по п.59, где антитело представляет собой моноклональное, биспецифическое или триспецифическое антитело.
61. Способ по п.60, где антитело представляет собой ритуксимаб.
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US201862633587P | 2018-02-21 | 2018-02-21 | |
US62/633,587 | 2018-02-21 | ||
PCT/US2019/018989 WO2019165097A1 (en) | 2018-02-21 | 2019-02-21 | Universal antigen presenting cells and uses thereof |
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