Publication Date

12-15-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-25-0197

PMID

41118265

PMCID

PMC12616409

PubMedCentral® Posted Date

11-15-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Chimeric antigen receptor (CAR)-engineered invariant NK T cells (CAR-NKT) are a novel cell platform for cancer immunotherapy. Unlike conventional T cells, NKTs are characterized by innate antitumor properties, minimal alloreactivity, and a unique ability to modulate the tumor microenvironment. This article provides a comprehensive overview of preclinical and early clinical studies evaluating CAR-NKTs in both autologous and allogeneic clinical settings. We discuss the contributions of CAR signaling domains, cytokine coexpression, and other functional measures that correlate with CAR-NKT persistence, function, and metabolic fitness. We also discuss the critical role of immunocompetent animal models in elucidating the interactions of CAR-NKTs with the tumor microenvironment and other components of the immune system. Finally, we review strategies that combine CAR-NKTs with other therapeutic approaches to promote potential synergistic benefits in patients with cancer.

Keywords

Humans, Receptors, Chimeric Antigen, Immunotherapy, Adoptive, Animals, Neoplasms, Tumor Microenvironment, Natural Killer T-Cells

Published Open-Access

yes

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