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:CAR-T Cell Therapy for T-Cell Malignancies.
CAR-T 细胞疗法已经彻底改变了B细胞淋巴系统肿瘤的治疗,并在某些情况下改善了疾病结局。
CAR-T 细胞疗法已经彻底改变了B细胞淋巴系统肿瘤的治疗,并在某些情况下改善了疾病结局。因此,六种FDA批准的靶向优先表达于恶性B细胞或浆细胞表面抗原的商用CAR-T细胞产品已被引入B细胞淋巴瘤、B-ALL和多发性骨髓瘤的治疗。这些治疗上的成功推动了CAR-T细胞疗法应用于其他血液系统肿瘤,包括T细胞恶性肿瘤。然而,CAR-T细胞疗法在T细胞肿瘤中的成功受到相当大的限制,原因在于存在一些限制因素,例如:1)正常T细胞与CAR-T细胞及恶性细胞之间共享相同抗原,导致自相残杀事件和严重T细胞发育不全;2)用于CAR转导的CAR-T细胞被恶性T细胞污染。异体CAR-T产品可以避免肿瘤污染,但会引发与免疫不相容性相关的其他问题。尽管存在这些局限性,过去几年中针对T细胞恶性肿瘤的CD7和CD5靶向CAR-T细胞疗法已取得显著进展。
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Thus, six FDA-approved commercial CAR-T cell products that target antigens preferentially expressed on malignant B-cells or plasma cells have been introduced in the therapy of B-cell lymphomas, B-ALLs, and multiple myeloma. These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies. However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited due to the existence of some limiting factors, such as: 1) the sharing of mutual antigens between normal T-cells and CAR-T cells and malignant cells, determining fratricide events and severe T-cell aplasia; 2) the contamination of CAR-T cells used for CAR transduction with malignant T-cells. Allogeneic CAR-T products can avoid tumor contamination but raise other problems related to immunological incompatibility. In spite of these limitations, there has been significant progress in CD7- and CD5-targeted CAR-T cell therapy of T-cell malignancies in the last few years.
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