Novel Approaches of Cellular Therapy in Multiple Myeloma: Focus on Chimeric Antigen Receptor T-Cells.

IF 1.7 4区医学 Q3 HEMATOLOGY

Acta Haematologica Pub Date : 2024-12-28 DOI:10.1159/000543265

Ravi Kishore Narra, Supriya Peshin, Binod Dhakal

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引用次数: 0

Abstract

Background: Recent advancements in cellular therapies, particularly chimeric antigen receptor T-cells (CAR-T) and T-cell-engaging bispecific antibodies have significantly altered the therapeutic landscape for multiple myeloma. There are two US FDA approved CAR-T products targeting BCMA available for commercial use at this time. Though these innovative therapies have demonstrated considerable efficacy in heavily pretreated multiple myeloma patients, many challenges remain, including accessibility, potential toxicities such as cytokine release syndrome and neurotoxicity and development of resistance through targeted antigen loss and T-cell exhaustion and various other mechanisms. CRISPR edited allogeneic CAR-T cells, CAR-NK cells, and structural makeover of autologous CART with safety switches are being studied to address current limitations in cellular therapy. Additionally, newer target antigens such as GPRC5D, FcRH5, armored CAR-T cells that resist immunosuppressive cytokines such as TGF-β are being investigated.

Summary: This review summarizes safety and efficacy of currently available CART, discusses challenges with these therapies, and ongoing research efforts aimed at addressing resistance, mitigate treatment-related toxicities, and refining for broader applicability and prolonged efficacy.

Key messages: CART cell therapy has shown significant benefit in treatment of multiple myeloma. Many challenges persist. Novel strategies with structural modifications are being incorporated to overcome the limitations.

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细胞治疗多发性骨髓瘤的新方法——以CART为重点。

背景：细胞疗法，尤其是 CAR-T 和 T 细胞参与双特异性抗体的最新进展极大地改变了多发性骨髓瘤的治疗格局。目前，美国 FDA 批准了两种针对 BCMA 的 CAR-T 产品用于商业用途。虽然这些创新疗法已在接受过大量预处理的多发性骨髓瘤患者中显示出相当大的疗效，但仍存在许多挑战，包括可及性、潜在毒性（如细胞因子释放综合征和神经毒性）以及通过靶向抗原丢失和 T 细胞耗竭及其他各种机制产生的抗药性。目前正在研究CRISPR编辑的异体CAR-T细胞、CAR- NK细胞以及带有安全开关的自体CART结构改造，以解决目前细胞疗法的局限性。此外，GPRC5D、FcRH5等新的靶抗原，以及能抵抗TGF-β等免疫抑制细胞因子的装甲CAR-T细胞也在研究之中。摘要：本综述总结了目前可用的CART的安全性和疗效，讨论了这些疗法面临的挑战，以及目前正在进行的旨在解决耐药性、减轻治疗相关毒性、完善更广泛适用性和延长疗效的研究工作：关键信息：CART细胞疗法在治疗多发性骨髓瘤方面疗效显著。许多挑战依然存在。为了克服这些局限性，我们正在采用结构调整的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Haematologica 医学-血液学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.