Adoptive transfer of tumor-infiltrating lymphocytes (TIL) or antigen-specific cytotoxic T lymphocytes (CTL) is safe and can be effective in cancer patients. Achievement of clinical responses in these patients is associated with the in vivo expansion and persistence of the transferred T lymphocytes. For this reason, recombinant human interleukin-2 (IL-2) is frequently used to support the in vivo survival of T lymphocytes infused into patients. However, IL-2 also causes important side effects. Thus, alternative strategies are highly demanded to limit cytokine-related off-target effects and to redirect the responsiveness of specific T-cell subsets to selected cytokines. Interleukin-7 (IL-7) is a promising alternative cytokine as it possesses the above mentioned properties. However, because its receptor is downregulated in ex vivo-expanded T cells, methods are required to restore their responsiveness to this homeostatic cytokine. In this chapter, we describe the methodology to obtain the ectopic expression of IL-7 receptor alpha (IL-7Rα) in antigenspecific CTL, using Epstein–Barr virus-specific CTL (EBV-CTL), as a model.
CITATION STYLE
Perna, S. K., Savoldo, B., & Dotti, G. (2014). Genetic modification of cytotoxic T lymphocytes to express cytokine receptors. Methods in Molecular Biology, 1139, 189–200. https://doi.org/10.1007/978-1-4939-0345-0_17
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