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嵌合抗原受体 T(CAR-T)细胞:血液系统恶性肿瘤的新型细胞治疗方法。

Chimeric antigen receptor T (CAR-T) cells: Novel cell therapy for hematological malignancies.

机构信息

Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.

Department of Clinical Immunology, Faculty of Medicine, The University of Manchester, Manchester, UK.

出版信息

Cancer Med. 2023 Apr;12(7):7844-7858. doi: 10.1002/cam4.5551. Epub 2022 Dec 30.

Abstract

Over the last decade, the emergence of several novel therapeutic approaches has changed the therapeutic perspective of human malignancies. Adoptive immunotherapy through chimeric antigen receptor T cell (CAR-T), which includes the engineering of T cells to recognize tumor-specific membrane antigens and, as a result, death of cancer cells, has created various clinical benefits for the treatment of several human malignancies. In particular, CAR-T-cell-based immunotherapy is known as a critical approach for the treatment of patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin's lymphoma (NHL). However, CAR-T-cell therapy of hematological malignancies is associated with various side effects. There are still extensive challenges in association with further progress of this therapeutic approach, from manufacturing and engineering issues to limitations of applications and serious toxicities. Therefore, further studies are required to enhance efficacy and minimize adverse events. In the current review, we summarize the development of CAR-T-cell-based immunotherapy and current clinical antitumor applications to treat hematological malignancies. Furthermore, we will mention the current advantages, disadvantages, challenges, and therapeutic limitations of CAR-T-cell therapy.

摘要

在过去的十年中,几种新型治疗方法的出现改变了人类恶性肿瘤的治疗前景。嵌合抗原受体 T 细胞(CAR-T)的过继免疫疗法,包括对 T 细胞进行工程改造以识别肿瘤特异性膜抗原,并由此导致癌细胞死亡,为治疗几种人类恶性肿瘤带来了各种临床益处。特别是,基于 CAR-T 细胞的免疫疗法被认为是治疗血液系统恶性肿瘤(如急性淋巴细胞白血病(ALL)、多发性骨髓瘤(MM)、慢性淋巴细胞白血病(CLL)、急性髓细胞白血病(AML)、霍奇金淋巴瘤(HL)和非霍奇金淋巴瘤(NHL))的关键方法。然而,CAR-T 细胞疗法治疗血液系统恶性肿瘤与各种副作用有关。从制造和工程问题到应用限制和严重毒性,进一步推进这种治疗方法仍然存在广泛的挑战。因此,需要进一步研究以提高疗效并最小化不良反应。在本综述中,我们总结了基于 CAR-T 细胞的免疫疗法的发展以及目前用于治疗血液系统恶性肿瘤的临床抗肿瘤应用。此外,我们将提到 CAR-T 细胞疗法的当前优势、劣势、挑战和治疗限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388d/10134288/92007df0d1ae/CAM4-12-7844-g003.jpg

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