CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR T-Cell therapy for the management of mantle cell lymphoma.
CAR T-Cell therapy for the management of mantle cell lymphoma.
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套细胞淋巴瘤(MCL)是成熟B细胞非霍奇金淋巴瘤亚型,通常由染色体易位导致Cyclin D1过表达。尽管对病因和治疗的认识不断进步,MCL仍无法治愈。高龄、男性、进展迅速、淋巴结广泛受累、血清乳酸脱氢酶升高,以及Ki-67高表达和TP53突变等均提示预后不佳。CAR-T 为B细胞恶性肿瘤和MCL患者提供了新的免疫治疗选择。靶向B细胞表面抗原已在其他B细胞肿瘤中获得显著应答,因此可用于复发/难治性MCL。美国FDA根据ZUMA-2试验结果批准brexucabtagene autoleucel(Tecartus,KTE-X19)治疗既往治疗无效或复发的MCL。严重不良反应、抗肿瘤活性中等、抗原丢失、肿瘤浸润及细胞迁移受限仍是重要障碍。本综述简要回顾CAR-T 治疗MCL的发展。
Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. Although with the progress in our knowledge of the causes for MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL.
Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed.
The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.
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