Abstract
γδ T cells have recently gained considerable attention as an attractive tool for cancer adoptive immunotherapy due to their potent anti-tumor activity and unique role in immunosurveillance. The remarkable success of engineered T cells for the treatment of hematological malignancies has revolutionized the field of adoptive cell immunotherapy. Accordingly, major efforts are underway to translate this exciting technology to the treatment of solid tumors and the development of allogeneic therapies. The unique features of γδ T cells, including their major histocompatibility complex (MHC)-independent anti-cancer activity, tissue tropism, and multivalent response against a broad spectrum of the tumors, render them ideal for designing universal ‘third-party’ cell products, with the potential to overcome the challenges of allogeneic cell therapy. In this review, we describe the crucial role of γδ T cells in anti-tumor immunosurveillance and we summarize the different approaches used for the ex vivo and in vivo expansion of γδ T cells suitable for the development of novel strategies for cancer therapy. We further discuss the different transduction strategies aiming at redirecting or improving the function of γδ T cells, as well as, the considerations for the clinical applications.
Highlights
Introduction γδT cells are the prototype of ‘unconventional’ T cells, containing a T cell receptor (TCR)composed of γ and δ chains with diverse structural and functional heterogeneity
The results showed no expansion of γδ T cells in the group treated with ZOL alone, whereas in the group treated with ZOL plus IL-2, 5/9 patients showed an increase in γδ T cells population and improved clinical outcome [66]
To avoid suboptimal activation of γδ T cells by pAgs in vivo, adoptive transfer of ex vivo expanded γδ T cells have been tested in several clinical trials and shown efficacy, though the number of γδ T cells still diminish over time
Summary
Human γδ T cells are divided into two main subsets based on their TCR usage of the Vδ1 chain or Vδ2 chain. Pellicci et al characterized a population of human T cells, named δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains They demonstrated that these cells, which represent. They recognize a broad spectrum of antigens on various cancer cells through their diverse innate cytotoxicity receptors expressed on their cell membrane [40] This broad response reduces the chances of tumor immune escape by single antigen loss. Using γδ T cells, either as a vehicle for chimeric antigen receptors (CARs) or αβ T cell-derived TCRs [43], may provide exciting results by combining tissue resident property and innate-like recognition of γδ T cells with antigen-specific activation and engagement of multiple costimulatory signals. The major obstacle to the broad application of γδ T cells for adoptive cell immunotherapy remains effective strategies of in vivo or ex vivo expansion [44,45]
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