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多发性骨髓瘤靶向免疫治疗新前沿的潜力抗原

英文原题:Promising Antigens for the New Frontier of Targeted Immunotherapy in Multiple Myeloma.

PubMed 2021/12/06(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

近年来多发性骨髓瘤(MM)治疗中新型药物的纳入改善了患者的临床结局。

中文摘要

近年来新型药物纳入多发性骨髓瘤(MM)治疗,改善了患者临床结局。特别是抗CD38单克隆抗体达雷妥尤单抗和抗SLAMF7单克隆抗体埃洛妥珠单抗获批用于复发或难治性MM(RRMM),是MM靶向免疫治疗发展的重要里程碑。这些单克隆抗体可通过多种依赖效应细胞的机制显著诱导MM细胞细胞毒作用,并进一步调节免疫,修复功能失调的肿瘤免疫微环境。近期,靶向MM特异性更强的B细胞成熟抗原(BCMA)疗法显示出强效活性,治疗形式包括CAR-T 细胞(CAR T)、抗体药物偶联物(ADC)、双特异性T细胞衔接器(BiTE)和双特异性抗体(BiAb);部分疗法已获批用于既往多线治疗的RRMM患者。新抗原孤儿G蛋白偶联受体C组5成员D(GPRC5D)和FcRH5也已被发现,并迅速进入临床研究。本文总结MM关键抗原的病理生物学功能及相应免疫疗法现状,并讨论潜在挑战和新兴治疗策略。

展开英文摘要原文

The incorporation of novel agents in recent treatments in multiple myeloma (MM) has improved the clinical outcome of patients. Specifically, the approval of monoclonal antibody (MoAb) against CD38 (daratumumab) and SLAMF7 (elotuzumab) in relapsed and refractory MM (RRMM) represents an important milestone in the development of targeted immunotherapy in MM. These MoAb-based agents significantly induce cytotoxicity of MM cells via multiple effector-dependent mechanisms and can further induce immunomodulation to repair a dysfunctional tumor immune microenvironment. Recently, targeting B cell maturation antigen (BCMA), an even MM-specific antigen, has shown high therapeutic activities by chimeric antigen receptor T cells (CAR T), antibody-drug conjugate (ADC), bispecific T-cell engager (BiTE), as well as bispecific antibody (BiAb), with some already approved for heavily pretreated RRMM patients. New antigens, such as orphan G protein-coupled receptor class C group 5 member D (GPRC5D) and FcRH5, were identified and rapidly moved to ongoing clinical studies. We here summarized the pathobiological function of key MM antigens and the status of the corresponding immunotherapies. The potential challenges and emerging treatment strategies are also discussed.

论文信息

作者
Cho SF、Xing L、Anderson KC、Tai YT
单位
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.Italy
文献类型
综述
期刊
Cancers2021 Dec 6
原文标识
PubMed 34885245 · DOI 10.3390/cancers13236136