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Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors

Abstract : Despite recent significant progress in cancer immunotherapies based on adoptive cell transfer(s)(ACT), the eradication of cancers still represents a major clinical challenge. In particular, the efficacy of current ACT-based therapies against solid tumors is dramatically reduced by physical barriers that prevent tumor infiltration of adoptively transferred effectors, and the tumor environment that suppress their anti-tumor functions. Novel immunotherapeutic strategies are thus needed to circumvent these issues. Human peripheral blood Vγ9Vδ2 T cells, a non-alloreactive innate-like T lymphocyte subset, recently proved to be a promising anti-tumor effector subset for ACT-based immunotherapies. Furthermore, new cell engineering tools that leverage the potential of CRISPR/Cas technology open astounding opportunities to optimize their anti-tumor effector functions. In this review, we present the current ACT strategies based on engineered T cells and their limitations. We then discuss the potential of engineered Vγ9Vδ2 T cell to overcome these limitations and improve ACT-based cancer immunotherapies.
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Submitted on : Monday, December 20, 2021 - 2:04:11 PM
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Chirine Rafia, Christelle Harly, Emmanuel Scotet. Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors. Immunological Reviews, Wiley, 2020, 298 (1), pp.117-133. ⟨10.1111/imr.12920⟩. ⟨inserm-03496227⟩



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