Antigen experience history directs distinct functional states of CD8⁺ CAR T cells during the antileukemia response.

ABSTRACT: Although chimeric antigen receptor (CAR) T cells are effective against B-lineage malignancies, post-CAR relapse is common, and efficacy in other tumors is limited. These challenges may be addressed through rational manipulations to control CAR T cell function. Here we examine the impact of cognate T cell antigen experience on subsequent CD8⁺ CAR T cell activity. Prior antigen encounter resulted in superior effector function against leukemia expressing low target antigen density at the expense of reduced proliferative capacity and susceptibility to dysfunction at limiting CAR doses. Distinctive temporal transcriptomic and epigenetic profiles in naive-derived and memory-derived CAR T cells identified RUNX family transcription factors as potential targets to augment the function of

SUBMITTER: DeGolier KR 

PROVIDER: S-EPMC11695263 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature