Characterization of Donor Variability for ?? T Cell ex vivo Expansion and Development of an Allogeneic ?? T Cell Immunotherapy.

ABSTRACT: Gamma delta (??) T cells recently emerged as an attractive candidate for cancer immunotherapy treatments due to their inherent cytotoxicity against both hematological and solid tumors. Moreover, ?? T cells provide a platform for the development of allogeneic cell therapies, as they can recognize antigens independent of MHC recognition and without the requirement for a chimeric antigen receptor. However, ?? T cell adoptive cell therapy depends on ex vivo expansion to manufacture sufficient cell product numbers, which remains challenging and limited by inter-donor variability. In the current study, we characterize the differences in expansion of ?? T cells from various donors that expand (EX) and donors that fail to expand, i.e., non-expanders (NE). Further, we demonstrate that IL-21 can be used to increase the expansion potential of NE. In order to reduce the risk of graft vs. host disease (GVHD) induced by an allogeneic T cell product, ?? T cell depletions must be considered due to the potential for HLA mismatch. Typically, ?? T cell depletions are performed at the end of expansion, prior to infusion. We show that ?? T cell cultures can be successfully ?? depleted on day 6 of expansion, providing a better environment for the ?? T cells to expand, and that the ?? T cell population remains below clinically acceptable standards for T cell-depleted allogeneic stem cell products. Finally, we assess the potential for a mixed donor ?? T cell therapy and characterize the effects of cryopreservation on ?? T cells. Collectively, these studies support the development of an improved allogeneic ?? T cell product and suggest the possibility of using mixed donor ?? T cell immunotherapies.

SUBMITTER: Burnham RE 

PROVIDER: S-EPMC7691424 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature