Bispecific antibodies and autologous chimeric antigen receptor T cell therapies for treatment of hematological malignancies.

IF 12.1 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Molecular Therapy Pub Date : 2024-08-07 Epub Date: 2024-05-31 DOI:10.1016/j.ymthe.2024.05.039
Samer Al Hadidi, Helen E Heslop, Malcolm K Brenner, Masataka Suzuki
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Abstract

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset of patients achieving prolonged disease control. This review explores the mechanisms underlying autologous CAR-T therapies and BsAbs, focusing on their clinical application in multiple myeloma, ALL, and non-Hodgkin lymphoma. We provide comprehensive insights into their individual efficacy, limitations concerning broad application, and the potential of combination therapies. These upcoming strategies aim to propel the field forward, paving the way for safer and more effective therapeutic interventions in hematological malignancies.

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治疗血液恶性肿瘤的双特异性抗体和自体嵌合抗原受体 T 细胞疗法。
近年来,血液恶性肿瘤的治疗领域取得了显著进展,尤其是自2017年首次批准自体嵌合抗原受体T细胞(CAR-T)疗法用于治疗复发/难治性急性淋巴细胞白血病(ALL)以来。自体CAR-T疗法涉及对患者的T细胞进行基因改造,以特异性识别和攻击癌细胞,而双特异性抗体(BsAbs)的功能是同时与癌细胞和免疫细胞结合,从而引发针对肿瘤的免疫反应。随后批准的各种 CAR-T 疗法和双特异性抗体彻底改变了多种血液恶性肿瘤的治疗,突出表现为高应答率和一部分患者实现了长期疾病控制。本综述探讨了自体 CAR-T 疗法和 BsAbs 的基本机制,重点关注它们在多发性骨髓瘤、ALL 和非霍奇金淋巴瘤中的临床应用。我们对它们各自的疗效、广泛应用的局限性以及联合疗法的潜力进行了全面深入的探讨。这些即将出台的策略旨在推动该领域的发展,为更安全、更有效的血液恶性肿瘤治疗干预铺平道路。
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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
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