T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity.

ABSTRACT:

Background

T cells modified to express a chimeric antigen receptor (CAR) are successful against B-lineage malignancies but fail to induce durable remissions in up to half of patients and have shown limited efficacy against other types of cancer. Strategies to improve CAR T cell potency and responses to low antigen densities without inducing CAR T cell dysfunction or limiting persistence are necessary to expand durability of remissions.

Methods

We overexpressed T-bet in human and mouse CAR T cells to mimic exposure to signal 3 cytokines during T cell priming to promote T helper cell 1 (Th1) polarization of CD4+CAR T cells with the goal of enhancing antitumor activity. Using human CAR T cells and xenograft models we interrogated the impact of T-bet overexpression on CAR T cell

SUBMITTER: Cimons JM 

PROVIDER: S-EPMC12007057 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature