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嵌合抗原受体 T 细胞疗法治疗套细胞淋巴瘤。

CAR T-Cell therapy for the management of mantle cell lymphoma.

机构信息

Department of Hematology, Ganzhou Key Laboratory of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Department of Pharmaceutics and Pharmaceutical Technology, L M College of Pharmacy, Ahmedabad, , 380009, Gujarat, India.

出版信息

Mol Cancer. 2023 Mar 31;22(1):67. doi: 10.1186/s12943-023-01755-5.

Abstract

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.

摘要

套细胞淋巴瘤(MCL)是一种成熟 B 细胞非霍奇金淋巴瘤(NHL)的亚型,其特征为易位,通常是由于 Cyclin D1 的过度表达。尽管随着我们对 MCL 病因和 MCL 可用治疗方法的了解不断进步,但这种癌症仍然无法治愈。年龄、男性、快速进展、明显的淋巴结受累、血清乳酸脱氢酶水平升高以及预后指标如 Ki-67 表达增加和 TP53 突变的存在,都是预后不良的标志。嵌合抗原受体(CAR)-T 细胞的高级免疫疗法对患有 B 细胞恶性肿瘤和 MCL 的患者有利。针对细胞表面的 B 细胞抗原是复发性(R/R)MCL 的一种可行方法,因为在其他 B 细胞癌症中已经获得了显著的反应。美国食品和药物管理局(FDA)已经批准了 brexucabtagene autoleucel(Tecartus,KTE-X19),这是一种新型的 CAR-T 细胞疗法,用于以前治疗无反应或复发的 MCL 患者。FDA 根据 ZUMA-2 临床试验的结果批准了这种新疗法。严重不良反应、中度抗肿瘤活性、过敏原撤退、抗原逃逸、有限的肿瘤浸润和运输是成功的 CAR-T 细胞疗法的主要障碍。这篇综述简要概述了 CAR-T 细胞治疗 MCL 的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302e/10064560/8788af065ea2/12943_2023_1755_Fig1_HTML.jpg

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