Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia, 420008.
Nazarbaev University, Qabanbay Batyr Ave 53, 010000, Astana, Kazakhstan.
Cancer Immunol Immunother. 2024 Nov 2;74(1):3. doi: 10.1007/s00262-024-03817-z.
The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest in the advancement of such therapeutic approaches. However, the efficacy of CAR-T cells against solid tumor cells has been limited due to the presence of various obstacles. Solid tumors exhibit antigenic diversity and an immunosuppressive microenvironment, which presents a challenge for immune cells attempting to penetrate the tumor. CAR-T cells also demonstrate decreased proliferative activity and cytotoxicity. Furthermore, concerns exist regarding tumor antigen loss and therapy-associated toxicity. Currently, scientists are working to enhance the structure of the CAR and improve the survival and efficiency of CAR-T cells in recognizing tumor antigens in solid tumors. Chemotherapy drugs are frequently employed in the treatment of malignant neoplasms and can also be used prior to cell therapy to enhance CAR-T cell engraftment. Recent studies have demonstrated that chemotherapy drugs can mitigate the suppressive impact of TME, eliminate the physical barrier by destroying the tumor stroma, and facilitate greater penetration of immune cells and CAR-T cells into the tumor. This, in turn, increases their survival, persistence, and cytotoxicity, as well as affects the metabolism of immune cells inside the tumor. However, the effectiveness of the combined approach against solid tumors depends on several factors, including the type of tumor, dosage, population of CAR-T cells, and individual characteristics of the body. This review examines the principal obstacles to the utilization of CAR-T cells against solid tumors, proposes solutions to these issues, and assesses the potential advantages of a combined approach to radiation exposure, which has the potential to enhance the sensitivity of the tumor to other agents.
嵌合抗原受体 (CAR)-T 细胞的应用增强了癌症治疗中可用治疗方式的范围。CAR-T 细胞在靶向清除血液癌细胞方面表现出相当大的疗效，从而激发了对这种治疗方法的大量兴趣。然而，由于存在各种障碍，CAR-T 细胞对实体瘤细胞的疗效受到限制。实体瘤表现出抗原多样性和免疫抑制微环境，这使得试图穿透肿瘤的免疫细胞面临挑战。CAR-T 细胞的增殖活性和细胞毒性也会降低。此外，还存在肿瘤抗原丢失和与治疗相关的毒性的问题。目前，科学家们正在努力增强 CAR 的结构，提高 CAR-T 细胞在识别实体瘤肿瘤抗原方面的生存能力和效率。化疗药物常用于治疗恶性肿瘤，也可在细胞治疗前使用，以增强 CAR-T 细胞的移植。最近的研究表明，化疗药物可以减轻 TME 的抑制作用，通过破坏肿瘤基质消除物理屏障，并促进更多的免疫细胞和 CAR-T 细胞进入肿瘤。这反过来又增加了它们的生存、持久性和细胞毒性，并影响肿瘤内免疫细胞的代谢。然而，联合方法对实体瘤的有效性取决于几个因素，包括肿瘤类型、剂量、CAR-T 细胞群体和个体身体特征。这篇综述探讨了 CAR-T 细胞在实体瘤应用中面临的主要障碍，提出了解决这些问题的方法，并评估了联合辐射暴露的潜在优势，这有可能提高肿瘤对其他药物的敏感性。
