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

Frontiers in Medicine

article

Rebecca E. Burnham¹  Christopher B. Doering¹  H. Trent Spencer¹  Jaquelyn T. Zoine¹  Jamie Y. Story¹  Swetha N. Garimalla⁴  Greg Gibson⁴  Aaron Rae¹  Erich Williams¹  Lisa Bixby¹  David Archer¹ 

[1] Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, United States;Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, United States;Cancer Biology Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, United States;School of Biological Sciences, Georgia Institute of Technology, United States

关键词: gamma delta (γδ) T cells;    allogeneic cell products;    ex vivo expanded T cells;    serum free expansion;    mixed cell product;   

DOI  :  10.3389/fmed.2020.588453

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY