CAR-iNKT 细胞肿瘤治疗：工程化、机制与临床进展综合综述

Chimeric antigen receptor (CAR)-modified T cells, as a revolutionary cancer immunotherapy, have achieved remarkable success in hematologic malignancies.

However, the therapy is hindered by severe toxicity, complex manufacturing, and suboptimal efficacy in solid tumors. Invariant natural killer T (iNKT) cells combine features of T cells and NK cells, bridging innate and adaptive immunity. Beyond direct cytotoxic functions, iNKT cells exert indirect antitumor effects through interactions with other immune cells while also modulating the tumor microenvironment (TME). Their exceptional TME infiltration capacity offers hope for solid tumor treatment. Leveraging their inherent major histocompatibility complex (MHC)-independent cytotoxicity, iNKT cells offer a viable strategy for developing "off-the-shelf" CAR cell products. Consequently, CAR-iNKT cell therapies developed by introducing CAR technology into iNKT cells demonstrate extraordinary potential as a next generation tumor immunotherapy.

Despite being established and garnering attention, CAR-iNKT cell therapy remains nascent with numerous obstacles. This review comprehensively discusses CAR-iNKT cell therapy, from the fundamental biology of iNKT cells to the latest advances in engineering and clinical translation, offering new perspectives for its research, development, and application.

A comprehensive literature search was conducted using [PubMed, Embase, and Web of Science] for articles published between [January 1900 and March 2026]. A groundbreaking technology known as chimeric antigen receptor (CAR) can turn a patient s own immune cells into formidable cancer-fighting warriors. CAR-T cell therapy has worked very well for blood cancers.

But it still has major problems: serious side effects, very high costs, long production times, and poor results against most solid tumors. Recently, scientists have started looking at another type of immune cell called invariant natural killer T (iNKT) cells. These cells are special because they can attack tumors directly, call other immune cells for help, and change the area around the tumor to make it less harmful. Most importantly, iNKT cells can go deep into solid tumors and do not need to be matched to a specific patient.

This means they can be made into ready-to-use treatments that are cheaper and faster to produce. By combining the power of CAR technology with iNKT cells, researchers have created a next-generation therapy called CAR-iNKT. Although this approach is still at an early stage and faces many challenges, it shows great promise. This paper provides an overview of the development, applications, and future prospects of this technology.