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Cancer Gene Ther ; 22(7): 360-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26182912

RESUMO

The ability to genetically modify T cells is a critical component to many immunotherapeutic strategies and research studies. However, the success of these approaches is often limited by transduction efficiency. As retroviral vectors require cell division for integration, transduction efficiency is dependent on the appropriate activation and culture conditions for T cells. Naive CD8(+) T cells, which are quiescent, must be first activated to induce cell division to allow genetic modification. To optimize this process, we activated mouse T cells with a panel of different cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-12, IL-15 and IL-23, known to act on T cells. After activation, cytokines were removed, and activated T cells were retrovirally transduced. We found that IL-12 preconditioning of mouse T cells greatly enhanced transduction efficiency, while preserving function and expansion potential. We also observed a similar transduction-enhancing effect of IL-12 preconditioning on human T cells. These findings provide a simple method to improve the transduction efficiencies of CD8(+) T cells.


Assuntos
Linfócitos T CD8-Positivos/fisiologia , Interleucina-12/farmacologia , Vírus da Leucemia Murina de Moloney/genética , Transdução Genética , Animais , Proteína 3 do Linfoma de Células B , Linfócitos T CD8-Positivos/efeitos dos fármacos , Células Cultivadas , Expressão Gênica , Humanos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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