基因修饰的 CAR-T 细胞疗法治疗血液系统恶性肿瘤。

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies.

机构信息

Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Department of Pediatrics, Division of Pediatric Immunology and Nephrology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

出版信息

Int J Mol Sci. 2020 Nov 17;21(22):8655. doi: 10.3390/ijms21228655.

Abstract

With advances in the understanding of characteristics of molecules, specific antigens on the surface of hematological malignant cells were identified and multiple therapies targeting these antigens as neoplasm treatments were developed. Among them, chimeric antigen receptor (CAR) T-cell therapy, which got United States Food and Drug Administration (FDA) approval for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) as well as for recurrent acute lymphoblastic leukemia (ALL) within the past five years, and for r/r mantle cell lymphoma (MCL) this year, represents one of the most rapidly evolving immunotherapies. Nevertheless, its applicability to other hematological malignancies, as well as its efficacy and persistence are fraught with clinical challenges. Currently, more than one thousand clinical trials in CAR T-cell therapy are ongoing and its development is changing rapidly. This review introduces the current status of CAR T-cell therapy in terms of the basic molecular aspects of CAR T-cell therapy, its application in hematological malignancies, adverse reactions during clinical use, remaining challenges, and future utilization.

摘要

随着对分子特征认识的提高,血液恶性肿瘤细胞表面的特定抗原被鉴定出来,多种针对这些抗原的治疗方法被开发出来作为肿瘤治疗方法。其中,嵌合抗原受体(CAR)T 细胞疗法在过去五年中获得了美国食品和药物管理局(FDA)的批准,用于治疗复发/难治性(r/r)弥漫性大 B 细胞淋巴瘤(DLBCL)以及复发性急性淋巴细胞白血病(ALL),今年也批准了 r/r 套细胞淋巴瘤(MCL),是最迅速发展的免疫疗法之一。然而,其在其他血液恶性肿瘤中的适用性、疗效和持久性都充满了临床挑战。目前,CAR T 细胞疗法正在进行的临床试验超过 1000 项,其发展变化迅速。本综述从 CAR T 细胞疗法的基本分子方面、其在血液恶性肿瘤中的应用、临床应用中的不良反应、尚存的挑战以及未来的应用等方面介绍了 CAR T 细胞疗法的现状。

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