Future perspectives on engineered T cells for cancer
Avery D. Posey, Regina M. Young, Carl H. June
Abstract
Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly T cell dysfunction and exhaustion. The heterogeneity and inhospitableness of the solid tumor microenvironment (TME) contribute to diminished CAR T cell efficacy exhibited by reduced cytotoxicity, proliferation, cytokine secretion, and the upregulation of inhibitory receptors, similar to the phenotype of tumor-infiltrating lymphocytes (TILs). In this review, we highlight recent advances in T cell therapy for solid tumors, particularly brain cancer. Innovative strategies, including locoregional delivery and 'armoring' CAR T cells with cytokines such as interleukin (IL)-18, are under investigation to improve efficacy and safety. We also highlight emerging issues with toxicity management of CAR T cell adverse events. This review discusses the obstacles associated with CAR T cell therapy in the context of solid tumors and outlines current and future strategies to overcome these challenges.