Altered cancer metabolism and implications for next-generation CAR T-cell therapies

• Published in: Pharmacology & therapeutics (Oxford) 2024-07, Vol.259, p.108667-108667, Article 108667
• Main Authors: Ramapriyan, Rishab, Vykunta, Vivasvan S., Vandecandelaere, Gust, Richardson, Leland G.K., Sun, Jing, Curry, William T., Choi, Bryan D.
• Format: Article
• Language: English
• Subjects: CAR T-cell therapy; CRISPR Cas systems; Immunotherapy; Metabolism; Solid tumors; Tumor microenvironment
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2024.108667

This review critically examines the evolving landscape of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors, with a particular focus on the metabolic challenges within the tumor microenvironment. CAR T-cell therapy has demonstrated remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited. A significant barrier is the hostile milieu of the tumor microenvironment, which impairs CAR T-cell survival and function. This review delves into the metabolic adaptations of cancer cells and their impact on immune cells, highlighting the competition for nutrients and the accumulation of immunosuppressive metabolites. It also explores emerging strategies to enhance CAR T-cell metabolic fitness and persistence, including genetic engineering and metabolic reprogramming. An integrated approach, combining metabolic interventions with CAR T-cell therapy, has the potential to overcome these constraints and improve therapeutic outcomes in solid tumors.