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

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 applicatio...

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Bibliographic Details
Published in:EBioMedicine Vol. 77; p. 103941
Main Authors: Gumber, Diana, Wang, Leo D.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.03.2022
Elsevier
Subjects:
Advanced Basic Science
Cancer
CAR T
Chimeric antigen receptor
Humans
Immunotherapy
Immunotherapy, Adoptive - methods
Internal Medicine
Receptors, Chimeric Antigen - therapeutic use
Review
T cell exhaustion
T-Lymphocytes
Tumor Microenvironment
T cell exhaustion
Chimeric antigen receptor
CAR T
Immunotherapy
Cancer
ISSN:2352-3964, 2352-3964
Online Access:Get full text
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Summary: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. Additionally, we discuss the potential of these strategies for improving clinical outcomes of CAR T cell therapy.
Bibliography:ObjectType-Article-1
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ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2022.103941