← 返回前沿论文

多发性骨髓瘤中的双特异性抗体:通过合理联合治疗最大化潜力

英文原题:Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies.

PubMed 2025/10/30(内容时间) Blood Rev Q1 · IF 7.2(JCR 2025)

研究概要

双特异性抗体已成为多发性骨髓瘤(MM)中一种变革性免疫治疗策略。

中文摘要

双特异性抗体已成为多发性骨髓瘤(MM)的一种变革性免疫治疗策略。早期BiTE构建体为后续药代动力学和安全性特征更佳的全长IgG抗体铺平了道路。截至2025年,teclistamab、elranatamab、linvoseltamab(均靶向BCMA×CD3)及talquetamab(靶向GPRC5D×CD3)已获批用于复发/难治性MM。靶向FcRH5的在研药物cevostamab,以及采用改变结合构型、靶向BCMA的新一代构建体,正在接受临床评估。尽管这些药物在后线治疗中应答率较高,但抗原丢失、T细胞功能障碍和可溶性BCMA介导的耐药仍是重大挑战。目前正在测试与IMiD、检查点抑制剂联合及双靶点策略,以增强疗效持久性。前线研究正在评估,将双特异性抗体纳入诱导治疗能否进一步加深应答并实现MRD阴性。随着临床数据积累,双特异性抗体有望重塑MM治疗,为部分患者提供一种现货型、可规模化且具有潜在治愈作用的CAR-T替代方案。

展开英文摘要原文

Bispecific antibodies have emerged as a transformative immunotherapeutic strategy in multiple myeloma (MM). Early constructs such as BiTEs paved the way for full-length IgG-based antibodies with improved pharmacokinetics and safety profiles. As of 2025, teclistamab, elranatamab, linvoseltamab (all BCMA CD3) and talquetamab (GPRC5D CD3) have received regulatory approval for relapsed/refractory MM. Investigational agents targeting FcRH5 (cevostamab) and next-generation constructs with altered binding configurations targeting BCMA are under clinical evaluation. Despite high response rates in late-line therapy, resistance via antigen loss, T-cell dysfunction and soluble BCMA presents a major challenge. Combinations with IMiDs, checkpoint inhibitors and dual-targeting approaches are being tested to enhance durability. Frontline studies currently investigate if bispecific antibodies can further deepen responses and induce MRD negativity when used as part of induction therapy. As clinical data matures, bispecific antibodies are likely to redefine MM treatment, by offering an off-the-shelf, scalable alternative to CAR-T therapy with curative potential in selected patient populations.

论文信息

作者
Zhou X、Waldschmidt JM、Einsele H
第一作者单位
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.Germany
通讯作者单位
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. Electronic address: einsele_h@ukw.de.Germany
文献类型
综述
期刊
Blood reviews2025 Nov
原文标识
PubMed 41177723 · DOI 10.1016/j.blre.2025.101342