Medical Center of Hematology, State Key Laboratory of Trauma, Burn and Combined Injury, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Cell Commun Signal. 2023 Aug 1;21(1):187. doi: 10.1186/s12964-023-01191-4.
Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem cells (MSCs). Recent studies have shown that MSCs can improve the anticancer functions of CAR-related products. CAR-MSCs can overcome the flaws of cellular immunotherapy. Thus, MSCs can be used as a biological vehicle for CARs. In this review, we first discuss the characteristics and immunomodulatory functions of MSCs. Then, the role of MSCs as a source of exosomes, including the characteristics of MSC-derived exosomes and their immunomodulatory functions, is discussed. The role of MSCs in CAR-related products, CAR-related product-derived exosomes and the effect of MSCs on CAR-related products are reviewed. Finally, the use of MSCs as CAR vehicles is discussed. Video Abstract.
嵌合抗原受体 (CARs) 被广泛应用于 T 细胞 (CAR-T 细胞)、自然杀伤细胞、树突状细胞和巨噬细胞中，在细胞免疫治疗中具有重要意义。然而，CAR 相关产品的应用面临着一些挑战，包括携带 CAR 的细胞持续时间短、细胞功能障碍或衰竭、疾病复发、免疫效应细胞相关神经毒性综合征、细胞因子释放综合征、对实体瘤疗效低以及肿瘤微环境的免疫抑制等。另一种重要的细胞治疗方案涉及间充质干细胞 (MSCs)。最近的研究表明，MSCs 可以改善 CAR 相关产品的抗癌功能。CAR-MSCs 可以克服细胞免疫治疗的缺陷。因此，MSCs 可以作为 CAR 的生物载体。在这篇综述中，我们首先讨论了 MSCs 的特征和免疫调节功能。然后，讨论了 MSCs 作为外泌体来源的作用，包括 MSC 衍生的外泌体的特征及其免疫调节功能。还综述了 MSCs 在 CAR 相关产品、CAR 相关产品衍生的外泌体以及 MSCs 对 CAR 相关产品的影响中的作用。最后，讨论了 MSCs 作为 CAR 载体的应用。视频摘要。
