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在多发性骨髓瘤中基于抗体和 CAR-T 细胞疗法的持续(R)革命:对 2022 年初未来的展望。

On the continuous (R)evolution of antibody-based and CAR T cell therapies in multiple myeloma: an early 2022 glance into the future.

机构信息

Molecular Oncology and Hematology Unit, Karl Landsteiner University of Health Sciences. Dr. Karl-Dorrek-Straße 30, 3500 Krems an der Donau, Austria.

Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, 3500 Krems an der Donau, Austria.

出版信息

Expert Opin Pharmacother. 2022 Aug;23(12):1425-1444. doi: 10.1080/14656566.2022.2101362. Epub 2022 Aug 10.

Abstract

INTRODUCTION

The pace at which the identification of novel therapeutic targets has led to the approval of multiple myeloma (MM) agents during the last two decades is nothing more than spectacular. Nevertheless, MM remains an incurable disease. Therefore, there is an urgent need for additional, innovative therapeutics. Immune dysfunction and the tumor-permissive immune bone marrow microenvironment represent hallmarks of MM pathophysiology. Naked monoclonal antibodies directed against SLAMF7 and CD38 already constitute backbones of today's MM therapy. Novel immunotherapeutic modalities including antibody-drug-conjugates (ADC), bispecific antibodies (BsAb), and chimeric-antigen-receptor T cells are on the way to once more revolutionize future MM therapy.

AREAS COVERED

The present review article summarizes the most recent results on MM immunotherapies presented at the 2021 Annual Meeting of the American Society of Hematology; and throws a glance on ongoing preclinical and clinical efforts aiming at further increasing their efficacy, while reducing their toxicity.

EXPERT OPINION

With the approvals of the first-in-class BCMA-targeting ADC (belantamab mafodotin) and two BCMA-targeting CAR T cell products (Ide-cel, Cilta-cel); and the approval of the first-in-class BCMAxCD3 BsAb immediately pending, the era of modern next-generation immunotherapies in MM is continuously evolving. Long-term disease-free survival and potential cure of MM are finally within reach.

摘要

简介

在过去的二十年中,新型治疗靶点的发现速度之快,使得多发性骨髓瘤(MM)药物的获批数量令人瞩目。然而,MM 仍然是一种无法治愈的疾病。因此,迫切需要额外的创新疗法。免疫功能障碍和肿瘤允许的骨髓免疫微环境是 MM 病理生理学的标志。针对 SLAMF7 和 CD38 的裸单抗已成为当今 MM 治疗的基础。新型免疫治疗方法包括抗体药物偶联物(ADC)、双特异性抗体(BsAb)和嵌合抗原受体 T 细胞,有望再次彻底改变未来的 MM 治疗。

涵盖领域

本文总结了在 2021 年美国血液学会年会上展示的最新 MM 免疫疗法研究结果,并展望了正在进行的临床前和临床研究工作,旨在提高其疗效,同时降低其毒性。

专家意见

随着首个 BCMA 靶向 ADC(belantamab mafodotin)和两种 BCMA 靶向 CAR T 细胞产品(Ide-cel、Cilta-cel)的获批,以及首个 BCMAxCD3 BsAb 的获批在即,MM 现代下一代免疫疗法的时代不断发展。MM 的无病长期生存和潜在治愈终于成为可能。

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