Treatment of children with either relapsed or refractory acute leukemia is still a major challenge. This explains the recent burst of immunotherapies.
In the allogeneic setting, γδ T cells represent a perfect candidate due to their ability to lyse tumor cells in a major histocompatibility complex (MHC)-independent manner, bypassing the occurrence of Graft-versus-Host Disease (GvHD). The majority of circulating γδ T cells are constituted of Vγ9Vδ2 cells, whereas a minor Vδ1 subset resides within the epithelial tissues.
Here, we developed a novel strategy for ex vivo expansion of both Vγ9Vδ2 and Vδ1 γδ T cells at a clinical-scale level with the ultimate goal of administering multiple infusions of such a cell product after allogeneic stem cell transplant.
We have previously demonstrated that in vitro exposure of γδ T cells to zoledronic acid (ZOL) combined with IL-2, allows robust expansion and activation of the Vδ2 subset alone. Herein, we developed a novel protocol for the expansion of both Vδ1 and Vδ2 by exploiting the mitogenic effect of Concanavalin-A (Con-A), together with ZOL and a cocktail of different cytokines.
Preliminary results obtained from 5 different healthy donors show that 1) we succeeded in expanding γδ T cells up to 50 folds, 2) the use of Con-A is essential for the Vδ1 subset expansion, 3) γδ T cells ex vivo expanded acquire an effector memory phenotype and are cytotoxic in vitro against pediatric acute leukemia cell lines. Therefore, these encouraging results lay the foundation for advancing the translational use of γδ T cells.