Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has emerged as a cancer treatment with enormous potential, demonstrating impressive antitumor activity in the treatment of hematological malignancies. However, CAR T cell exhaustion is a major limitation to their efficacy, particularly in the application of CAR T cells to solid tumors. CAR T cell exhaustion is thought to be due to persistent antigen stimulation, as well as an immunosuppressive tumor microenvironment, and mitigating exhaustion to maintain CAR T cell effector function and persistence and achieve clinical potency remains a central challenge. Here, we review the underlying mechanisms of exhaustion and discuss emerging strategies to prevent or reverse exhaustion through modifications of the CAR receptor or CAR independent pathways.

SUBMITTER: Gumber D 

PROVIDER: S-EPMC8927848 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature