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

ABSTRACT: Chimeric antigen receptor T cells are an effective therapy for B-lineage malignancies. However, many patients relapse and this therapeutic has yet to show strong efficacy in other hematologic or solid tumors. One opportunity for improvement lies in the ability to generate T cells with desirable functional characteristics. Here, we dissect the biology of CD8+ CAR T cells (CAR8) by controlling whether the T cell has encountered cognate TCR antigen prior to CAR generation. We find that prior antigen experience influences multiple aspects of in vitro and in vivo CAR8 functionality, resulting in superior effector function and leukemia clearance in the setting of limiting target antigen density compared to antigen-inexperienced T cells. However, this comes at the expense of inferio

SUBMITTER: DeGolier KR 

PROVIDER: S-EPMC10775394 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature