Department of Chemistry, Biochemistry, University of Washington, Seattle, WA 98105, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Curr Pharm Biotechnol. 2024;25(15):2001-2011. doi: 10.2174/0113892010265228231116073012.
Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a revolutionary approach for cancer treatment, especially for hematologic cancers. However, CAR-T therapy has some limitations, including cytokine release syndrome (CRS), immune cellassociated neurologic syndrome (ICANS), and difficulty in targeting solid tumors and delivering allogeneic cell therapy due to graft--host disease (GvHD). Therefore, it is important to explore other cell sources for CAR engineering. Invariant natural killer T (iNKT) cells are a potential target, as they possess powerful antitumor ability and do not recognize mismatched major histocompatibility complexes (MHCs) and protein antigens, thus avoiding the risk of GvHD. CAR-engineered iNKT (CAR-iNKT) cell therapy offers a promising new approach to cancer immunotherapy by overcoming the drawbacks of CAR-T cell therapy while retaining potent antitumor capabilities. This review summarizes the current CAR-iNKT cell products, their functions and phenotypes, and their potential for off-the-shelf cancer immunotherapy.
嵌合抗原受体 (CAR)-修饰的 T (CAR-T) 细胞疗法已成为癌症治疗的一种革命性方法，特别是在血液系统癌症方面。然而，CAR-T 疗法存在一些局限性，包括细胞因子释放综合征 (CRS)、免疫细胞相关神经综合征 (ICANS)，以及由于移植物抗宿主病 (GvHD) 而难以靶向实体瘤和进行同种异体细胞治疗。因此，探索其他 CAR 工程细胞来源非常重要。不变自然杀伤 T (iNKT) 细胞是一个潜在的靶点，因为它们具有强大的抗肿瘤能力，并且不识别错配的主要组织相容性复合体 (MHC) 和蛋白质抗原，从而避免了 GvHD 的风险。CAR 修饰的 iNKT (CAR-iNKT) 细胞疗法通过克服 CAR-T 细胞疗法的缺点，同时保留强大的抗肿瘤能力，为癌症免疫疗法提供了一种有前途的新方法。本综述总结了目前的 CAR-iNKT 细胞产品、它们的功能和表型，以及它们在现货型癌症免疫疗法中的潜力。
