RU2411040C2 - Композиции и способы для лечения опухолей, презентирующих антигены сурвивина - Google Patents

Композиции и способы для лечения опухолей, презентирующих антигены сурвивина Download PDF

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RU2411040C2
RU2411040C2 RU2008114624/10A RU2008114624A RU2411040C2 RU 2411040 C2 RU2411040 C2 RU 2411040C2 RU 2008114624/10 A RU2008114624/10 A RU 2008114624/10A RU 2008114624 A RU2008114624 A RU 2008114624A RU 2411040 C2 RU2411040 C2 RU 2411040C2
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Стефен Д. ДЖИЛЛИЗ (US)
Стефен Д. Джиллиз
Тор А. О. ХЕТТМАНН (DE)
Тор А. О. ХЕТТМАНН
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Паскаль Андре Стейн
Стефан Джи КЛАЙНЦ (US)
Стефан Джи КЛАЙНЦ
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Abstract

Изобретение относится к биотехнологии. Описана вакцина, вызывающая у человека иммунный ответ на сурвивин человека, содержащая пептид или нуклеиновую кислоту, кодирующую пептид, происходящий от мутированного сурвивина курицы, содержащего BIR-домен, имеющий 50%-90% аминокислотную идентичность BIR-домену, располагающемуся от Asp16 до Leu87 в сурвивине человека и содержащему мутации N97E, Т99М, V100L и Q101G, которые способствуют презентации антигена Т-клеткам путем связывания с молекулами МНС, причем указанный пептид возможно слит с Fc-группировкой. Изобретение расширяет арсенал средств для лечения опухолей, сверхэкспрессирующих сурвивин. 3 н. и 14 з.п. ф-лы, 15 ил., 3 табл.

Description

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Claims (17)

1. Вакцина, вызывающая у человека иммунный ответ на сурвивин человека, содержащая:
(а) пептид или нуклеиновую кислоту, кодирующую пептид, происходящий от мутированного сурвивина курицы, который (i) имеет последовательность SEQ ID NO:12, (ii) содержит BIR-домен, имеющий 50-90% аминокислотную идентичность BIR-домену, располагающемуся от Asp 16 до Leu87 в сурвивине человека, и (iii) содержит мутации N97E, Т99М, V100L и Q101G, которые способствуют презентации антигена Т-клеткам путем связывания с молекулами МНС, причем указанный пептид возможно слит с Fc-групппировкой, и
(б) возможно адъювант.
2. Вакцина по п.1, где сурвивин курицы содержит мутацию внутри BIR-домена, которая, по существу, уничтожает биологическую активность, приписываемую BIR-домену.
3. Вакцина по п.2, где указанная мутация уничтожает антиапоптическую активность BIR-домена.
4. Вакцина по п.2, где указанный пептид, происходящий от указанного сурвивина курицы, содержит аминокислотную замену в одной или более чем одной из позиций, соответствующих Arg18, Pro47, Cys57, Cys60, His77 и Cys84 сурвивина человека.
5. Вакцина по п.1, где вакцина способна активировать Т-клетки, распознающие последовательность пептида сурвивина человека в комплексе с молекулой МНС.
6. Вакцина по п.1, включающая цитокин, выбранный из группы, состоящей из IL-2, IL-7, IL-12, IL-18, IL-21, IL-23 и GM-CSF.
7. Вакцина по п.1, где нуклеиновая кислота, кодирующая указанный пептид, содержит промотор млекопитающих.
8. Вакцина по п.7, где нуклеиновая кислота представляет собой голую ДНК (naked DNA).
9. Вакцина по п.1, где нуклеиновая кислота приготовлена в виде препарата с реагентом, который повышает трансфекцию клеток млекопитающих.
10. Вакцина по п.1, где нуклеиновая кислота представляет собой часть вирусной частицы.
11. Вакцина по п.10, где вирусная частица представляет собой аденовирусную частицу.
12. Вакцина по п.1, где вакцина содержит бактерию, содержащую указанную нуклеиновую кислоту.
13. Вакцина по п.12, где бактерия представляет собой Salmonella.
14. Вакцина по п.1 для применения в способе иммунизации человека против опухолевых клеток, сверхэкспрессирующих сурвивин человека.
15. Вакцина по п.1 для применения в лечении опухолей, сверхэкспрессирующих сурвивин человека.
16. Вакцина, вызывющая у человека иммунный ответ на сурвивин человека, содержащая:
(а) мутированный сурвивин курицы, содержащий мутации N97E, Т99М, V100L и Q101G и имеющий аминокислотную последовательность SEQ ID NO:12, где указанные мутации способствуют презентации антигена Т-клеткам путем связывания с молекулами МНС, и сурвивин курицы содержит BIR-домен, имеющий 50-90% аминокислотную идентичность BIR-домену, располагающемуся от Asp 16 до Leu87 в сурвивине человека, и
(б) возможно адъювант
для применения в лечении рака легких.
17. Фармацевтическая композиция, вызывющая иммунный ответ на сурвивин человека, содержащая вакцину по любому из пп.1-13, возможно вместе с приемлемым носителем, разбавителем или эксципиентом.
RU2008114624/10A 2005-09-27 2006-09-27 Композиции и способы для лечения опухолей, презентирующих антигены сурвивина RU2411040C2 (ru)

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