Targeting CAR-T cell exhaustion in non-Hodgkin lymphoma: mechanistic insights and emerging clinical strategies

Frontiers in Immunology 2026 Open access

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Authors: A K Rao, Christina Darwish, Kerry S. Campbell, Rashmi Khanal, Henry Fung, Anthony Stack
DOI: 10.3389/fimmu.2026.1727926
Cited by: 1
References: 176

Abstract

Although the response rates to chimeric antigen receptor T (CAR-T) therapy in patients with treatment-resistant lymphoma are high, the majority of patients relapse. CAR-T cell exhaustion, characterized by the progressive loss of T-cell effector functions due to several molecular and epigenetic pathways, is a major mediator of CAR-T cell failure. Strategies to prevent CAR-T cell exhaustion, including modifications to the CAR structure, addition of adjunctive agents, and alternative product manufacturing strategies have shown promise. In this review, we discuss the mechanisms of CAR-T cell exhaustion and describe strategies for its mitigation, with the aim of supporting further research in this critical area.

Fields of Study & Subjects

CAR-T cell therapy research Lymphoma Diagnosis and Treatment Monoclonal and Polyclonal Antibodies Research

Publication details

Journal / source
Frontiers in Immunology
Publisher
Frontiers Media SA
Volume
17
Pages
1727926–1727926
Publication date
21 April 2026
Language
EN