Current progress in chimeric antigen receptor T-cell therapy for malignant tumors

Yashang Zheng, Jiaqian Huang, Yuhong Xu, Hui-Yan Luo
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Abstract

In the realm of malignant tumor treatment, particularly regarding hematologic malignancies, chimeric antigen receptor T-cell (CAR-T) immunotherapy has witnessed remarkable advancements in recent years. This approach involves genetically modifying and engineering a patient's T-cells ex vivo to express a specific CAR, known as CAR-T cells. When these modified cells are reintroduced into the patient, they can specifically recognize target antigens and exhibit highly efficient cytotoxicity against cells expressing these antigens, making them suitable for the treatment of malignant tumors. CD19, which is expressed on the surface of B lymphocytes at different stages of differentiation, has been identified as a suitable target for the treatment of most B-cell lymphomas. CAR-T cells targeting CD19 have demonstrated excellent specificity, cytotoxicity, and persistence in both in vitro and clinical trials, showing tremendous potential for application. However, identifying appropriate targets for CAR-T therapy in solid tumors remains a challenge, leading to limited advancements in this area. This review discusses the mechanisms, applications, limitations, and prospects of CAR-T therapy in hematologic malignancies and solid tumors, aiming to provide directions for future research in this field.

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嵌合抗原受体 T 细胞疗法治疗恶性肿瘤的最新进展
在恶性肿瘤治疗领域,尤其是血液系统恶性肿瘤方面,嵌合抗原受体 T 细胞(CAR-T)免疫疗法近年来取得了显著进展。这种方法涉及对患者体内的 T 细胞进行基因修饰和工程改造,使其表达特定的 CAR,即 CAR-T 细胞。当这些经过修饰的细胞被重新输入患者体内时,它们可以特异性识别目标抗原,并对表达这些抗原的细胞表现出高效的细胞毒性,从而使它们适用于治疗恶性肿瘤。CD19 表达于处于不同分化阶段的 B 淋巴细胞表面,已被确定为治疗大多数 B 细胞淋巴瘤的合适靶点。以 CD19 为靶点的 CAR-T 细胞在体外和临床试验中都表现出极佳的特异性、细胞毒性和持久性,显示出巨大的应用潜力。然而,为实体瘤的 CAR-T 疗法确定合适的靶点仍是一项挑战,导致该领域的进展有限。本综述讨论了CAR-T疗法在血液恶性肿瘤和实体瘤中的机制、应用、局限性和前景,旨在为该领域的未来研究提供方向。
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