Future perspectives on engineered T cells for cancer.

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.
Competing Interests: Declaration of interests C.H.J. is an inventor of patents related to the CAR therapy product that is the subject of this review, as well as other CAR therapy products, and may be eligible to receive a select portion of royalties paid from Kite to the University of Pennsylvania. C.H.J. is a scientific cofounder and holds equity in Capstan Therapeutics, Dispatch Biotherapeutics, and Bluewhale Bio. C.H.J. serves on the board of AC Immune and is a scientific adviser to BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Cellcarta, Celldex, Danaher, Decheng, ImmuneSensor, Kite, Marble Therapeutics, Poseida, Verismo, Viracta, ViTToria, and WIRB-Copernicus group. C.H.J., A.D.P., and R.M.Y. are inventors on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and Kite and may receive license revenue from such licenses.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)