4.6 Review

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

Journal

IMMUNOLOGICAL REVIEWS
Volume 298, Issue 1, Pages 117-133

Publisher

WILEY
DOI: 10.1111/imr.12920

Keywords

ACT; CAR T cells; CRISPR; engineering; solid tumor; V gamma 9V delta 2 T cells

Categories

Funding

  1. Association pour la Recherche contre le Cancer [PJA 20191209404]
  2. Ligue Contre le Cancer [AOGO2019]
  3. Association pour la Recherche sur le Cancer [PJA20191209404]
  4. Fondation pour la Recherche Medicale [FRM DEQ20170839118]

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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 V gamma 9V delta 2 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 V gamma 9V delta 2 T cell to overcome these limitations and improve ACT-based cancer immunotherapies.

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