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CD81 costimulation skews CAR transduction toward naive T cells.

Liora M SchultzDebra K CzerwinskiRonald LevyShoshana Levy
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Adoptive cellular therapy using chimeric antigen receptors (CARs) has revolutionized our treatment of relapsed B cell malignancies and is currently being integrated into standard therapy. The impact of selecting specific T cell subsets for CAR transduction remains under investigation. Previous studies demonstrated that effector T cells derived from naive, rather than central memory T cells mediate more potent antitumor effects. Here, we investigate a method to skew CAR transduction toward naive T cells without physical cell sorting. Viral-mediated CAR transduction requires ex vivo T cell activation, traditionally achieved using antibody-mediated strategies. CD81 is a T cell costimulatory molecule that when combined with CD3 and CD28 enhances naive T cell activation. We interrogate the effect of CD81 costimulation on resultant CAR transduction. We identify that upon CD81-mediated activation, naive T cells lose their identifying surface phenotype and switch to a memory phenotype. By prelabeling naive T cells and tracking them through T cell activation and CAR transduction, we document that CD81 costimulation enhanced naive T cell activation and resultantly generated a CAR T cell product enriched with naive-derived CAR T cells.
Keyphrases
  • hiv infected
  • cell therapy
  • nk cells
  • working memory
  • physical activity
  • sars cov
  • acute lymphoblastic leukemia
  • mental health
  • regulatory t cells
  • antiretroviral therapy
  • single cell
  • anti inflammatory