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

Autor: Ramapriyan R; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: rramapriyan@mgh.harvard.edu., Vykunta VS; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Medical Scientist Training Program, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA., Vandecandelaere G; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Richardson LGK; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Sun J; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Curry WT; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Choi BD; Brain Tumor Immunotherapy Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: bchoi@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Pharmacology & therapeutics [Pharmacol Ther] 2024 Jul; Vol. 259, pp. 108667. Date of Electronic Publication: 2024 May 17.
DOI: 10.1016/j.pharmthera.2024.108667
Abstrakt: 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.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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