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1.
Cancer Gene Ther ; 22(7): 360-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26182912

RESUMEN

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.


Asunto(s)
Linfocitos T CD8-positivos/fisiología , Interleucina-12/farmacología , Virus de la Leucemia Murina de Moloney/genética , Transducción Genética , Animales , Proteínas del Linfoma 3 de Células B , Linfocitos T CD8-positivos/efectos de los fármacos , Células Cultivadas , Expresión Génica , Humanos , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
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