Combined PD-L1 and TIM3 blockade improves expansion of fit human CD8⁺ antigen-specific T cells for adoptive immunotherapy.

ABSTRACT: Antigen-specific T cell expansion ex vivo followed by adoptive transfer enables targeting of a multitude of microbial and cancer antigens. However, clinical-scale T cell expansion from rare precursors requires repeated stimulation, which may lead to T cell dysfunction and limited therapeutic potential. We used a clinically compliant protocol to expand Epstein-Barr virus (EBV) and Wilms tumor 1 (WT1) antigen-specific CD8⁺ T cells, and leveraged T cell exhaustion-associated inhibitory receptor blockade to improve T cell expansion. Several inhibitory receptors were expressed early by ex vivo-expanded antigen-specific CD8⁺ T cells, including PD-1 and TIM3, with co-expression matching evidence of T cell dysfunction as the cultures progressed. Introduction of

SUBMITTER: Lak S 

PROVIDER: S-EPMC9593254 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature