决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Expanding the Horizon of CAR-T Cell Therapy: Present Obstacles and New Strategies for Future CARs in Solid Tumors.
嵌合抗原受体(CAR)-T细胞是用于识别特定抗原的合成受体,这些抗原由重编程的T细胞表达以靶向肿瘤。
嵌合抗原受体(CAR)-T 细胞是用于识别由重编程 T 细胞表达的特定抗原以靶向肿瘤的合成受体。CAR-T 细胞疗法在治疗血液系统恶性肿瘤方面取得了显著临床成功,如慢性淋巴细胞白血病(CLL)、套细胞淋巴瘤(MCL)、弥漫性大 B 细胞淋巴瘤(DLBCL)、淋巴浆细胞淋巴瘤(LPL)和原发性眼内淋巴瘤(PIL)。由于其在白血病和淋巴瘤癌症中的显著成功,越来越多的临床前研究和临床试验正致力于将 CAR-T 细胞疗法扩展到实体瘤。然而,CAR-T 疗法仍存在一些局限性,包括缺乏可靶向抗原多样性、抗原表达异质性、T 细胞运输效率不足以及免疫抑制性肿瘤微环境。本综述探讨了 CAR-T 细胞疗法的作用、当前挑战以及针对实体瘤恶性肿瘤的新兴解决方案。为克服 CAR-T 细胞疗法现有的局限性,已设计出创新策略,包括优化带有检查点抑制剂的新型 CAR 载体,以增强 CAR-T 细胞对实体瘤的抗肿瘤活性。本综述还探讨了新型 CAR-T 细胞的设计以及提高对实体瘤抗肿瘤活性的策略。在新兴策略中,通用 CAR 和与检查点抑制剂的联合方法对于将 CAR-T 疗法扩展到实体瘤尤其有前景。
Chimeric antigen receptor (CAR)-T cells are synthetic receptors used for the recognition of specific antigens expressed by reprogrammed T cells for targeting tumors. CAR-T cell therapy has gained remarkable clinical success for the treatment of hematological malignancies such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), lymphoplasmacytic lymphoma (LPL), and primary intraocular lymphoma (PIL). The increasing number of preclinical investigations and clinical trials is focusing on extending CAR-T cell therapy to solid tumors due to its remarkable success in leukemia and lymphoma cancers. However, some limitations of CAR-T therapy still exist, including a lack of targetable antigen diversity, heterogeneous antigen expression, insufficient T-cell trafficking efficiency, and an immunosuppressive tumor microenvironment. This review explores the role of CAR-T cell therapy, current challenges, and emerging solutions for solid tumor malignancies. To overcome the existing limitations of CAR-T cell therapy, innovative strategies, including the optimization of novel CAR vectors with checkpoint inhibitors, have been designed to enhance the antitumor activity of CAR-T cells against solid tumors. It also explores the design of novel CAR-T cells and strategies for improving antitumor activity against solid tumors. Among the emerging strategies, universal CARs and combination approaches with checkpoint inhibitors are especially promising for extending CAR-T therapy to solid tumors.
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