肿瘤细胞治疗研究
英文原题：Engineered T Cells: CAR T Cell Therapy and Beyond.
目前，已有四款嵌合抗原受体（CAR）T 细胞产品获批：axicabtagene ciloleucel、tisagenlecleucel、lisocabtagene maraleucel 和 brexucabtagene autoleucel。
综述目的：本文回顾非霍奇金淋巴瘤中工程化T细胞疗法（包括CAR T细胞疗法）的现有数据和未来方向。 近期进展：目前已有四种嵌合抗原受体（CAR）T细胞产品获批：axicabtagene ciloleucel、tisagenlecleucel、lisocabtagene maraleucel和brexucabtagene autoleucel。这些产品在构建、适应证、制备、临床试验设计和毒性特征方面各不相同，但均为靶向CD19的自体细胞产品。在这些产品用于其他B细胞淋巴瘤亚型方面也出现令人鼓舞的早期数据。其他工程化T细胞产品也在研发中，包括靶向CD19/CD22的双靶点CAR T细胞、靶向CD30的CAR T细胞、异基因CAR T细胞和工程化自然杀伤（NK）细胞。新型CAR构建体的临床前数据也显示出前景，包括分泌细胞因子的CAR、靶向T细胞受体恒定区（TRAC）基因座的基因递送、联合策略和第三代CAR。CAR T细胞已改变复发/难治性B细胞淋巴瘤患者的治疗格局。新型工程化细胞产品的早期数据令人鼓舞，有望在未来进入临床应用。
PURPOSE OF REVIEW: This article reviews the current data and future directions of engineered T cell therapies in non-Hodgkin lymphomas. RECENT FINDINGS: Currently, four chimeric antigen receptor (CAR) T cell products are approved: axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel. These products differ in construct, indication, manufacturing, clinical trial design, and toxicity profile, but all are autologous products targeting CD19. Encouraging early data is also emerging with the use of these products in additional subtypes of B cell lymphoma. Alternative engineered T cell products are also in development, including dual CD19/22 targeting CAR T cells, CD30-directed CAR T cells, allogeneic CAR T cells, and engineered natural killer (NK) cells. Preclinical data using novel CAR constructs such as cytokine-secreting CARs targeted gene delivery into the T cell receptor constant (TRAC) locus, combination strategies, and third-generation CARs holds promise for additional novel approaches. CAR T cells have transformed the therapeutic landscape for patients with relapsed/refractory B cell lymphomas. Early data with novel engineered cellular products is encouraging and holds promise for future clinical use.
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