γδ T Cell-Based Adoptive Cell Therapies Against Solid Epithelial Tumors

Abstract

Conventionally, adoptive cell therapies have been developed and optimized using αβ T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell-based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of discussion in the field, pertaining to their use in adoptive immunotherapy. We aimed to compile information about γδ T-cell enhancement in terms of expansion, phenotype, and inhibitory receptors, in addition to the latest advances in preclinical and clinical research using γδ T cells specifically against solid epithelial tumors.

Figure 1:. Strategies for expansion of Vδ1 and Vδ2 T cells

(A) Illustrates the expansion of Vδ1 T cells using an initial cocktail of IL-4, IFN-γ, IL-21, IL-1β, and OKT3, followed by further supplementation with IL-15 (without IL-4), resulting in a highly pure γδ T cell population (mean of 98%, n=8). Cellular proportions and resulting phenotypic markers are derived from data corresponding to 8 individual donors from Almeida et al., 2016. (B) Displays the different protocols used to increase the number of Vδ2 and their cytotoxicity during ex vivo expansion. Markers related with an optimal effector phenotype are described on the right (28,33,66-68,75,76,78,81)