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RU2010116757A - Угнетение опухолей с помощью плацентарного перфузата человека и выделенных из плаценты человека вспомогательных натуральных клеток-киллеров - Google Patents

Угнетение опухолей с помощью плацентарного перфузата человека и выделенных из плаценты человека вспомогательных натуральных клеток-киллеров Download PDF

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RU2010116757A
RU2010116757A RU2010116757/15A RU2010116757A RU2010116757A RU 2010116757 A RU2010116757 A RU 2010116757A RU 2010116757/15 A RU2010116757/15 A RU 2010116757/15A RU 2010116757 A RU2010116757 A RU 2010116757A RU 2010116757 A RU2010116757 A RU 2010116757A
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Сяокуй ЧЖАН (US)
Сяокуй ЧЖАН
Ванесса. А ВОСКИНАРЯН-БЕРСЕ (US)
Ванесса. А ВОСКИНАРЯН-БЕРСЕ
Линь КАН (US)
Линь КАН
Нирав Дилип ПАДЛИЯ (US)
Нирав Дилип ПАДЛИЯ
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Селджин Селльюлар Терапьютикс (Us)
Селджин Селльюлар Терапьютикс
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Abstract

1. Композиция, содержащая человеческие клетки плацентарного перфузата, для использования в способе подавления пролиферации опухолевых клеток in vivo или in vitro. ! 2. Композиция по п.1, где опухолевыми клетками являются клетки рака крови. ! 3. Композиция по п.1, где опухолевыми клетками являются клетки солидной опухоли. ! 4. Композиция по п.1, где опухолевыми клетками являются клетки первичной карциномы из эпителия протоков, клетки лейкоза, клетки острого Т-клеточного лейкоза, клетки хронической миелоидной лимфомы (CML), клетки острого миелогенного лейкоза, клетки хронического миелогенного лейкоза (CML), клетки легочной карциномы, клетки аденокарциномы ободочной кишки, клетки гистиоцитарной лимфомы, клетки колоректальной карциномы, клетки колоректальной аденокарциномы или клетки ретинобластомы. ! 5. Композиция по п.1, где указанное подавление происходит в условиях in vitro. ! 6. Композиция по п.1, где указанное подавление происходит в условиях in vivo. ! 7. Композиция по п.6, где указанное подавление происходит в человеке. ! 8. Композиция по п.1, где указанное множество клеток плацентарного перфузата представляет собой совокупность ядросодержащих клеток из плацентарного перфузата. ! 9. Композиция по п.1, где указанные клетки плацентарного перфузата подвергнуты обработке для удаления, по меньшей мере, одного типа клеток. ! 10. Композиция по п.1, где указанные клетки плацентарного перфузата подвергнуты обработке с тем, чтобы обогатить, по меньшей мере, одним типом клеток. ! 11. Композиция по п.1, где указанные клетки плацентарного перфузата содержат, по крайней мере, приблизительно 50% клеток CD56+ плаценты. ! 12. Композиция, содержащая выделенные CD

Claims (25)

1. Композиция, содержащая человеческие клетки плацентарного перфузата, для использования в способе подавления пролиферации опухолевых клеток in vivo или in vitro.
2. Композиция по п.1, где опухолевыми клетками являются клетки рака крови.
3. Композиция по п.1, где опухолевыми клетками являются клетки солидной опухоли.
4. Композиция по п.1, где опухолевыми клетками являются клетки первичной карциномы из эпителия протоков, клетки лейкоза, клетки острого Т-клеточного лейкоза, клетки хронической миелоидной лимфомы (CML), клетки острого миелогенного лейкоза, клетки хронического миелогенного лейкоза (CML), клетки легочной карциномы, клетки аденокарциномы ободочной кишки, клетки гистиоцитарной лимфомы, клетки колоректальной карциномы, клетки колоректальной аденокарциномы или клетки ретинобластомы.
5. Композиция по п.1, где указанное подавление происходит в условиях in vitro.
6. Композиция по п.1, где указанное подавление происходит в условиях in vivo.
7. Композиция по п.6, где указанное подавление происходит в человеке.
8. Композиция по п.1, где указанное множество клеток плацентарного перфузата представляет собой совокупность ядросодержащих клеток из плацентарного перфузата.
9. Композиция по п.1, где указанные клетки плацентарного перфузата подвергнуты обработке для удаления, по меньшей мере, одного типа клеток.
10. Композиция по п.1, где указанные клетки плацентарного перфузата подвергнуты обработке с тем, чтобы обогатить, по меньшей мере, одним типом клеток.
11. Композиция по п.1, где указанные клетки плацентарного перфузата содержат, по крайней мере, приблизительно 50% клеток CD56+ плаценты.
12. Композиция, содержащая выделенные CD56+, CD16- вспомогательные натуральные клетки-киллеры плаценты (PINK) для использования в способе подавления пролиферации опухолевых клеток in vivo или in vitro, где PINK клетки экспрессируют одну или несколько молекул микроРНК hsa-miR-100, hsa-miR-127, hsa-miR-211, hsa-miR-302c, hsa-miR-326, hsa-miR-337, hsa-miR-497, hsa-miR-512-3р, hsa-miR-515-5p, hsa-miR-517b, hsa-miR-517c, hsa-miR-518a, hsa-miR-518e, hsa-miR-519d, hsa-miR-520g, hsa-miR-520h, hsa-miR-564, hsa-miR-566, hsa-miR-618 и/или hsa-miR-99a с детектируемым более высоким уровнем, чем натуральные клетки-киллеры периферической крови.
13. Композиция по п.12, где указанное подавление происходит в условиях in vitro.
14. Композиция по п.12, где указанное подавление происходит в условиях in vivo.
15. Композиция по п.14, где указанное подавление происходит в человеке.
16. Композиция по п.12, где указанными опухолевыми клетками являются клетки первичной карциномы из эпителия протоков, клетки лейкоза, клетки острого Т-клеточного лейкоза, клетки хронической миелоидной лимфомы (CML), клетки острого миелогенного лейкоза, клетки хронического миелогенного лейкоза (CML), клетки легочной карциномы, клетки аденокарциномы ободочной кишки, клетки гистиоцитарной лимфомы, клетки множественной миеломы, клетки колоректальной карциномы, клетки колоректальной аденокарциномы или клетки ретинобластомы.
17. Композиция по п.12, где указанные PINK клетки контактировали с количеством иммуномодулирующего соединения и в течение времени которые достаточны для того, чтобы указанные PINK клетки экспрессировали детектируемое большее количество гранзима В, чем эквивалентное число PINK клеток, которые не контактировали с указанным иммуномодулирующим соединением.
18. Композиция по п.17, где указанным иммуномодулирующим соединением является леналидомид или помалидомид.
19. Композиция по п.12, где указанные PINK клетки контактировали с количеством иммуномодулирующего соединения и в течение времени которые достаточны для того, чтобы указанные PINK клетки проявляли детектируемую большую цитотоксичность по отношению к указанным опухолевым клеткам, чем эквивалентное число PINK клеток, которые не контактировали с указанным иммуномодулирующим соединением.
20. Композиция по п.19, где указанным иммуномодулирующим соединением является леналидомид или помалидомид.
21. Композиция по п.17 или 19, где указанные PINK клетки экспрессируют один или несколько из ВАХ, CCL5, CCR5, CSF2, FAS, GUSB, IL2RA или TNFRSF18 с более высоким уровнем, чем эквивалентное число PINK клеток, которые не контактировали с указанным иммуномодулирующим соединением.
22. Композиция по п.17 или 19, где указанные PINK клетки экспрессируют один или несколько из АСТВ, ВАХ, CCL2, CCL3, CCL5, CCR5, CSF1, CSF2, ЕСЕ1, FAS, GNLY, GUSB, GZMB, IL1A, IL2RA, IL8, IL10, LTA, PRF1, PTGS2, SKI и ТВХ21 с более высоким уровнем, чем эквивалентное число PINK клеток, которые не контактировали с указанным иммуномодулирующим соединением.
23. Композиция по п.12, содержащая комбинированные натуральные клетки-киллеры, где указанные комбинированные натуральные клетки-киллеры включают указанные PINK клетки и натуральные клетки-киллеры, выделенные из пуповинной крови, и где пуповинную кровь выделяют из плаценты, из которой получают указанные PINK клетки.
24. Композиция по п.23, где указанные комбинированные натуральные клетки-киллеры включают:
детектируемое большее число натуральных клеток-киллеров CD3-CD56+CD16-, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое меньшее число натуральных клеток-киллеров CD3-CD56+CD16+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+KIR2DL2/L3+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое меньшее число натуральных клеток-киллеров CD3-CD56+NKp46+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+NKp30+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+2B4+, чем эквивалентное число натуральных клеток-киллеров из периферической крови; или
детектируемое большее число натуральных клеток-киллеров CD3-CD56+CD94+, чем эквивалентное число натуральных клеток-киллеров из периферической крови.
25. Композиция по п.23, где указанные комбинированные натуральные клетки-киллеры включают:
детектируемое меньшее число натуральных клеток-киллеров CD3-CD56+KIR2DL2/L3+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+NKp46+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+NKp44+, чем эквивалентное число натуральных клеток-киллеров из периферической крови;
детектируемое большее число натуральных клеток-киллеров CD3-CD56+NKp30+, чем эквивалентное число натуральных клеток-киллеров из периферической крови.
RU2010116757/15A 2007-09-28 2008-09-29 Угнетение опухолей с помощью плацентарного перфузата человека и выделенных из плаценты человека вспомогательных натуральных клеток-киллеров RU2536242C2 (ru)

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