RU2010130993A - Способы улучшения направленного воздействия на cd138-экспрессирующие опухолевые клетки и агенты для их осуществления - Google Patents

Способы улучшения направленного воздействия на cd138-экспрессирующие опухолевые клетки и агенты для их осуществления Download PDF

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RU2010130993A
RU2010130993A RU2010130993/10A RU2010130993A RU2010130993A RU 2010130993 A RU2010130993 A RU 2010130993A RU 2010130993/10 A RU2010130993/10 A RU 2010130993/10A RU 2010130993 A RU2010130993 A RU 2010130993A RU 2010130993 A RU2010130993 A RU 2010130993A
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tumor cells
adhesion
cytotoxic agent
immunoconjugate
inhibits
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RU2010130993/10A
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RU2486203C2 (ru
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Бенжамин ДЕЛКЕН (DE)
Бенжамин ДЕЛКЕН
Кристоф УЭРЕК (DE)
Кристоф УЭРЕК
Кеннет АНДЕРСОН (US)
Кеннет АНДЕРСОН
Теру ХИДЕСИМА (US)
Теру ХИДЕСИМА
Кристоф БРЮХЕР (DE)
Кристоф БРЮХЕР
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Биотест Аг (De)
Биотест Аг
Иммуноджен, Инк. (Us)
Иммуноджен, Инк.
Дана-Фарбер Кэнсер Инститьют, Инк. (Us)
Дана-Фарбер Кэнсер Инститьют, Инк.
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Abstract

1. Способ уменьшения адгезии стромальных клеток к CD138-экспрессирующим опухолевым клеткам в опухолевых клетках нуждающегося субъекта, который включает: ! введение в указанные опухолевые клетки иммуноконъюгата против CD138-экспрессирующих опухолевых клеток в количестве, эффективном для уменьшения адгезии стромальных клеток к CD138-экспрессирующим опухолевым клеткам, и, необязательно, введение в указанные опухолевые клетки дополнительного цитотоксического средства в количестве, ингибирующем, задерживающем и/или предотвращающем рост опухолевых клеток. ! 2. Способ по п.1, в котором указанный иммуноконъюгат включает эффекторную молекулу и агент против клетки-мишени, причем указанная эффекторная молекула и указанный агент против клетки-мишени связаны друг с другом при помощи расщепляемого линкера. ! 3. Способ по п.2, в котором расщепляемый линкер содержит дисульфидную связь. ! 4. Способ по п.3, в котором линкер является SPP или SPDB. ! 5. Способ по любому из пп.1-4, в котором адгезия уменьшена, по меньшей мере, примерно на 10%, примерно на 20%, примерно на 30%, примерно на 40%, примерно на 50%, примерно на 60%, примерно на 70%, примерно на 80% или больше. ! 6. Способ по любому из пп.1-4, в котором указанная уменьшенная адгезия вызывает ослабление опосредуемой адгезией устойчивости к лекарствам. ! 7. Способ по п.6, в котором уменьшена опосредуемая адгезией устойчивость к лекарствам в отношении дополнительного цитотоксического средства, не являющегося указанным иммуноконъюгатом, и в котором указанное дополнительное цитотоксическое средство вводят в количестве, ингибирующем, задерживающем и/или предотвращающем рост опухолевых клеток. ! 8. Способ по

Claims (18)

1. Способ уменьшения адгезии стромальных клеток к CD138-экспрессирующим опухолевым клеткам в опухолевых клетках нуждающегося субъекта, который включает:
введение в указанные опухолевые клетки иммуноконъюгата против CD138-экспрессирующих опухолевых клеток в количестве, эффективном для уменьшения адгезии стромальных клеток к CD138-экспрессирующим опухолевым клеткам, и, необязательно, введение в указанные опухолевые клетки дополнительного цитотоксического средства в количестве, ингибирующем, задерживающем и/или предотвращающем рост опухолевых клеток.
2. Способ по п.1, в котором указанный иммуноконъюгат включает эффекторную молекулу и агент против клетки-мишени, причем указанная эффекторная молекула и указанный агент против клетки-мишени связаны друг с другом при помощи расщепляемого линкера.
3. Способ по п.2, в котором расщепляемый линкер содержит дисульфидную связь.
4. Способ по п.3, в котором линкер является SPP или SPDB.
5. Способ по любому из пп.1-4, в котором адгезия уменьшена, по меньшей мере, примерно на 10%, примерно на 20%, примерно на 30%, примерно на 40%, примерно на 50%, примерно на 60%, примерно на 70%, примерно на 80% или больше.
6. Способ по любому из пп.1-4, в котором указанная уменьшенная адгезия вызывает ослабление опосредуемой адгезией устойчивости к лекарствам.
7. Способ по п.6, в котором уменьшена опосредуемая адгезией устойчивость к лекарствам в отношении дополнительного цитотоксического средства, не являющегося указанным иммуноконъюгатом, и в котором указанное дополнительное цитотоксическое средство вводят в количестве, ингибирующем, задерживающем и/или предотвращающем рост опухолевых клеток.
8. Способ по п.7, в котором указанное цитотоксическое средство представляет собой мефалан, винкристин, доксорубицин, дексаметазон, циклофосфамид, этопозид, цитарабин, цисплатин, талидомид, прендизон, бортезомиб, леналидомид, сорафениб, ромидепсин или их комбинации.
9. Способ по п.7, в котором цитотоксическое средство создано на основе антитела.
10. Способ по п.1 или 2, в котором указанная эффекторная молекула имеет стерическое препятствие.
11. Способ по п.1 или 2, в котором эффекторная молекула представляет собой, по меньшей мере, один майтанзиноид, таксан, СС1065 или их аналог.
12. Способ по п.11, в котором эффекторная молекула представляет собой, по меньшей мере, один майтанзиноид, такой как DM1, DM3 или DM4.
13. Способ по п.12, в котором указанная эффекторная молекула представляет собой DM4.
14. Способ по любому из пп.1-4, в котором указанный агент против клетки-мишени иммуноконъюгата включает:
аминокислотную последовательность тяжелой цепи иммуноглобулина или ее части, где указанная тяжелая цепь иммуноглобулина или ее части, по меньшей мере, на 70%, по меньшей мере, на 80%, по меньшей мере, на 90%, по меньшей мере, на 85% или, по меньшей мере, на 98% идентичны SEQ ID NO:1.
15. Способ по п.7, в котором иммуноконъюгат и цитотоксическое средство вводят последовательно, где цитотоксическое средство вводят после введения иммуноконъюгата.
16. Способ по п.7, в котором иммуноконъюгат и цитотоксическое средство вводят одновременно.
17. Способ по любому из пп.1-4 и 7-9, в котором указанный субъект является раковым пациентом, страдающим одним из следующих заболеваний: множественная миелома, карцинома яичника, карцинома почки, карцинома желчного пузыря, карцинома молочной железы, рак предстательной железы, рак легкого, карцинома толстой кишки, лимфома Ходжкина и неходжкинская лимфома, хронический лимфолейкоз (CLL), острый лимфобластный лейкоз (ALL), острый миелобластный лейкоз (AML) и солидная тканевая саркома.
18. Способ по п.17, в котором указанный пациент страдает множественной миеломой.
RU2010130993/10A 2007-12-26 2008-12-23 Способы улучшения направленного воздействия на cd138-экспрессирующие опухолевые клетки и агенты для их осуществления RU2486203C2 (ru)

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Effective date: 20191224