摘要
多发性骨髓瘤(multiple myeloma, MM)是一种以恶性浆细胞增殖为特征的血液系统肿瘤。目前,蛋白酶体抑制剂(proteasome inhibitors, PIs)、免疫调节剂(immunomodulatory drugs, IMiDs)和自体造血干细胞移植(autologous hematopoietic stem cell transplantation, ASCT)是改善MM患者生存预后的主要手段,但随着治疗的深入,大多数患者仍面临难治和复发问题,治愈之路依然充满挑战。近年来,单克隆抗体(monoclonal antibodies, mAbs)、嵌合抗原受体T细胞(chimeric antigen receptor T-cells, CAR-T)、抗体药物耦联物(antibody-drug conjugates, ADCs)和双特异性抗体(bispecific antibodies, BsAbs)均在临床研究和/或临床应用中取得了良好的疗效,这些基于抗体和细胞的免疫治疗为难治复发性MM(refractory and relapsed multiple myeloma, RRMM)患者带来了新的希望。各类免疫治疗产品在激活免疫细胞、靶向肿瘤以及改善患者预后方面各有优势,但同时也面临安全性和耐药性的挑战。未来,随着分子生物学和抗体工程技术的不断进步,新型免疫治疗产品有望通过联合疗法等多种策略实现协同增效,从而为RRMM患者带来更长久的生存获益和生活质量的改善。本文旨在综述多发性骨髓瘤免疫治疗的研究成果与现存挑战,探讨单克隆抗体、CAR-T、抗体药物耦联物和双特异性抗体的作用机制、临床应用现状及未来发展趋势,为相关领域研究者和临床医生提供一个全面和系统的参考,推动MM精准免疫治疗的发展。
Multiple myeloma(MM)is a hematologic malignancy characterized by the malignant proliferation of plasma cells.Currently,proteasome inhibitors(PIs),immunomodulatory drugs(IMiDs),and autologous hematopoietic stem cell transplantation(ASCT)are the primary approaches used to improve the survival outcomes of MM patients.However,as treatment advances,most patients still face refractory and relapsed diseases,and the path to a cure remains challenging.In recent years,monoclonal antibodies(mAbs),chimeric antigen receptor T cells(CAR-T),antibody-drug conjugates(ADCs),and bispecific antibodies(BsAbs)have all demonstrated promising efficacy in clinical studies and applications.These antibody and cell-based immunotherapies have brought new hope to patients with refractory and relapsed MM(RRMM).Each type of immunotherapy offers unique advantages in activating immune cells,targeting tumors,and improving patient outcomes,yet they also encounter challenges related to safety and resistance.In the future,with continuous advancements in molecular biology and antibody engineering,novel immunotherapeutic products are expected to achieve synergistic effects through combination strategies,thereby providing longer survival benefits and improved life quality for RRMM patients.This article aims to review the latest progress in immunotherapy for MM,systematically discussing the mechanisms of action,current clinical applications,and future development trends of mAbs,CAR-T,ADCs,and BsAbs.It is intended to serve as a comprehensive reference for researchers and clinicians and promote advancing precision immunotherapy for MM.
作者
王萌
孙春艳
WANG Meng;SUN Chun-Yan(Department of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
出处
《中国生物化学与分子生物学报》
北大核心
2025年第6期774-782,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金面上项目(No.82270214,82470205)资助。
关键词
多发性骨髓瘤
免疫治疗
单克隆抗体
嵌合抗原受体T细胞
抗体药物耦联物
双特异性抗体
multiple myeloma(MM)
immunotherapy
monoclonal antibodies(mAbs)
chimeric antigen receptor T-cells(CAR-T)
antibody-drug conjugates(ADCs)
bispecific antibodies(BsAbs)
