RU2012111349A - Генерация линий ctl со специфичностью против множества опухолевых антигенов или множества вирусов - Google Patents

Генерация линий ctl со специфичностью против множества опухолевых антигенов или множества вирусов Download PDF

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RU2012111349A
RU2012111349A RU2012111349/10A RU2012111349A RU2012111349A RU 2012111349 A RU2012111349 A RU 2012111349A RU 2012111349/10 A RU2012111349/10 A RU 2012111349/10A RU 2012111349 A RU2012111349 A RU 2012111349A RU 2012111349 A RU2012111349 A RU 2012111349A
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Russia
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antigen
individual
population
viruses
lymphocytes
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RU2012111349/10A
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English (en)
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Анн Мари ЛИН
Клиона РУНИ
Ульрике ГЕРДЕМАНН
Хуан ВЕРА
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Байлор Колледж Оф Медсин
Уилсон Вулф Мэньюфэкчуринг
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Publication of RU2012111349A publication Critical patent/RU2012111349A/ru

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Abstract

1. Способ генерации цитотоксических Т-лимфоцитов (CTL), которые нацелены по меньшей мере на один антиген двух или более вирусов, включающий стадии:или(1) нуклеофекции популяции дендритных клеток (DC) от индивидуума множеством плазмид, где каждая плазмида множества кодирует по меньшей мере один антиген одного из двух или более вирусов, и, таким образом, продуцирует популяцию дендритных клеток, которая экспрессирует и презентирует по меньшей мере один антиген двух или более вирусов;или(2) контактирования популяции DC от индивидуума с библиотекой пептидов, где пептиды перекрываются в последовательности, чтобы охватывать часть или весь полный вирусный антиген, продуцируя, таким образом, популяцию DC (APC), которая презентирует по меньшей мере один эпитоп двух или более различных антигенов; иконтактирования мононуклеарных клеток периферической крови (РВМС) индивидуума с DC, подвергнутыми нуклеофекции (АРС), для получения популяции антиген-специфичных Т-лимфоцитов, которые способны отвечать по меньшей мере на один антиген двух или более вирусов; икультивирования антиген-специфичных Т-лимфоцитов в среде в сосуде, который имеет газопроницаемую мембрану, где компоненты среды включают IL-4 и IL-7, для получения цитотоксических Т-лимфоцитов (CTL), которые нацелены по меньшей мере на один антиген двух или более вирусов.2. Способ по п.1, в котором CTL вводят иммуноскомпрометированному индивидууму.3. Способ по п.2, в котором индивидуум имел трансплантацию аллогенных стволовых клеток.4. Способ по п.1, в котором вирусы выбраны из группы, состоящей из EBV, CMV, аденовируса, ВК, HHV6, RSV, гриппа, парагриппа, бокавируса, коронавируса, LCMV, вируса эпидемичес�

Claims (11)

1. Способ генерации цитотоксических Т-лимфоцитов (CTL), которые нацелены по меньшей мере на один антиген двух или более вирусов, включающий стадии:
или
(1) нуклеофекции популяции дендритных клеток (DC) от индивидуума множеством плазмид, где каждая плазмида множества кодирует по меньшей мере один антиген одного из двух или более вирусов, и, таким образом, продуцирует популяцию дендритных клеток, которая экспрессирует и презентирует по меньшей мере один антиген двух или более вирусов;
или
(2) контактирования популяции DC от индивидуума с библиотекой пептидов, где пептиды перекрываются в последовательности, чтобы охватывать часть или весь полный вирусный антиген, продуцируя, таким образом, популяцию DC (APC), которая презентирует по меньшей мере один эпитоп двух или более различных антигенов; и
контактирования мононуклеарных клеток периферической крови (РВМС) индивидуума с DC, подвергнутыми нуклеофекции (АРС), для получения популяции антиген-специфичных Т-лимфоцитов, которые способны отвечать по меньшей мере на один антиген двух или более вирусов; и
культивирования антиген-специфичных Т-лимфоцитов в среде в сосуде, который имеет газопроницаемую мембрану, где компоненты среды включают IL-4 и IL-7, для получения цитотоксических Т-лимфоцитов (CTL), которые нацелены по меньшей мере на один антиген двух или более вирусов.
2. Способ по п.1, в котором CTL вводят иммуноскомпрометированному индивидууму.
3. Способ по п.2, в котором индивидуум имел трансплантацию аллогенных стволовых клеток.
4. Способ по п.1, в котором вирусы выбраны из группы, состоящей из EBV, CMV, аденовируса, ВК, HHV6, RSV, гриппа, парагриппа, бокавируса, коронавируса, LCMV, вируса эпидемического паротита, вируса кори, метапневмовируса, парвовируса В, ротавируса, вируса Западного Нила и их комбинаций.
5. Способ по п.2, в котором клетки вводят путем инъекции.
6. Способ по п.5, в котором инъекция является внутривенной.
7. Способ генерации цитотоксических Т-лимфоцитов (CTL), которые нацелены на два или более опухолевых антигенов, включающий стадии:
или
(1) нуклеофекции популяции DC от индивидуума множеством плазмид, где каждая плазмида множества кодирует по меньшей мере один эпитоп одного или более опухолевых антигенов, продуцируя, таким образом, популяцию DC (APC), которая экспрессирует и презентирует по меньшей мере один эпитоп двух или более опухолевых антигенов;
или
(2) контактирования популяции DC от индивидуума с библиотекой пептидов, где пептиды перекрываются в последовательности, чтобы охватывать часть или весь полный антиген, продуцируя, таким образом, популяцию DC (APC), которая презентирует по меньшей мере один эпитоп двух или более различных антигенов; и
контактирования мононуклеарных клеток периферической крови (РВМС) индивидуума с АРС, для получения популяции антиген-специфичных Т-лимфоцитов, которые способны отвечать по меньшей мере на один эпитоп двух или более опухолевых антигенов; и
культивирования Т-лимфоцитов в среде в сосуде, который имеет газопроницаемую мембрану, где компоненты среды включают IL7, IL12, IL15 и или IL6, или IL27.
8. Способ по п.7, в котором индивидуум имеет лимфому или лейкоз.
9. Способ по п.7, в котором Т-лимфоциты вводят индивидууму.
10. Способ по п.9, в котором клетки вводят путем инъекции.
11. Способ по п.10, в котором инъекция является внутривенной.
RU2012111349/10A 2009-08-24 2010-08-24 Генерация линий ctl со специфичностью против множества опухолевых антигенов или множества вирусов RU2012111349A (ru)

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