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

• Type of Material: Article
• Authors: Rebecca E. Burnham, Emory University; Jaquelyn T. Zoine, Emory University; Jamie Story, Emory University; Swetha N. Garimalla, Georgia Institute of Technology; Gregory Gibson, Emory University; Aaron Rae, Emory University; Erich Williams, Emory University; Lisa Bixby, Emory University; David Archer, Emory University; Christopher Doering, Emory University; H Trent Spencer, Emory University
• Language: English
• Date: 2020-11-14
• Publisher: Springer Verlag
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Burnham, Zoine, Story, Garimalla, Gibson, Rae, Williams, Bixby, Archer, Doering and Spencer.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fmed.2020.588453
• Title of Journal or Parent Work: Frontiers of Medicine
• Volume: 7
• Grant/Funding Information: These studies were funded by Curing Kids Cancer, the NIH-NCI Grant No. 5R21CA223300, and the Peachbowl Legacy Foundation.
• Keywords: serum free expansion; mixed cell product; gamma delta (γδ) T cells; allogeneic cell products; ex vivo expanded T cells
• Research Categories: Biology, Cell; Health Sciences, Rehabilitation and Therapy; Health Sciences, Immunology

Abstract

Gamma delta (γδ) T cells recently emerged as an attractive candidate for cancer immunotherapy treatments due to their inherent cytotoxicity against both hematological and solid tumors. Moreover, γδ 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, γδ 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 γδ 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, αβ T cell depletions must be considered due to the potential for HLA mismatch. Typically, αβ T cell depletions are performed at the end of expansion, prior to infusion. We show that γδ T cell cultures can be successfully αβ depleted on day 6 of expansion, providing a better environment for the γδ T cells to expand, and that the αβ 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 γδ T cell therapy and characterize the effects of cryopreservation on γδ T cells. Collectively, these studies support the development of an improved allogeneic γδ T cell product and suggest the possibility of using mixed donor γδ T cell immunotherapies.