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IL-12 conditioning improves retrovirally mediated transduction efficiency of CD8+ T cells

Cancer Gene Therapy volume 22, pages 360–367 (2015)Cite this article

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Abstract

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.

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Acknowledgements

We thank Dan Neitzke for critical review of this manuscript. We thank Gina Scurti (Loyola University) for expert technical advice in culturing human T cells. Grant funding for this project was provided by P01CA54778-01 from the National Institutes of Health and the National Cancer Institute. This work was also supported in part by the Cell Evaluation and Therapy Shared Resource, Hollings Cancer Center and Medical University of South Carolina (P30CA138313). We also acknowledge the NIH Tetramer Core Facility (Contract No. HHSN272201300006C) for provision of the tetramer used in this study.

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Authors and Affiliations

  1. Department of Surgery, Medical University of South Carolina, Charleston, SC, USA

    K Andrijauskaite, S Suriano, C A Cloud, M Li, P Kesarwani, C M Paulos, S Mehrotra, D J Cole & M P Rubinstein

  2. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA

    L S Stefanik, C M Paulos, S Mehrotra, D J Cole & M P Rubinstein

  3. Loyola University Chicago, Maywood, IL, USA

    K M Moxley

  4. Immunology and Biotechnology Division, Faculty of Science, Tanta University, Tanta, Egypt

    M L Salem

  5. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA

    E Garrett-Mayer

  6. Experimental Transplantation and Immunology Branch , National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    J N Kochenderfer

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  1. K Andrijauskaite
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Correspondence to M P Rubinstein.

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Andrijauskaite, K., Suriano, S., Cloud, C. et al. IL-12 conditioning improves retrovirally mediated transduction efficiency of CD8+ T cells. Cancer Gene Ther 22, 360–367 (2015). https://doi.org/10.1038/cgt.2015.28

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