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双特异性抗体:多发性骨髓瘤治疗的新时代。

Bispecific Antibodies: A New Era of Treatment for Multiple Myeloma.

作者信息

Zhou Xiang, Einsele Hermann, Danhof Sophia

机构信息

Department of internal medicine II, University Hospital Würzburg, Oberdürrbacher Street 6, D-97080 Würzburg, Germany.

出版信息

J Clin Med. 2020 Jul 9;9(7):2166. doi: 10.3390/jcm9072166.

Abstract

Despite the introduction of novel agents such as proteasome inhibitors, immunomodulatory drugs, and autologous stem cell transplant, multiple myeloma (MM) largely remains an incurable disease. In recent years, monoclonal antibody-based treatment strategies have been developed to target specific surface antigens on MM cells. Treatment with bispecific antibodies (bsAbs) is an immunotherapeutic strategy that leads to an enhanced interaction between MM cells and immune effector cells, e.g., T-cells and natural killer cells. With the immune synapse built by bsAbs, the elimination of MM cells can be facilitated. To date, bsAbs have demonstrated encouraging results in preclinical studies, and clinical trials evaluating bsAbs in patients with MM are ongoing. Early clinical data show the promising efficacy of bsAbs in relapsed/refractory MM. Together with chimeric antigen receptor-modified (CAR)-T-cells, bsAbs represent a new dimension of precision medicine. In this review, we provide an overview of rationale, current clinical development, resistance mechanisms, and future directions of bsAbs in MM.

摘要

尽管引入了蛋白酶体抑制剂、免疫调节药物和自体干细胞移植等新型药物,但多发性骨髓瘤(MM)在很大程度上仍然是一种无法治愈的疾病。近年来,已开发出基于单克隆抗体的治疗策略,以靶向MM细胞上的特定表面抗原。双特异性抗体(bsAbs)治疗是一种免疫治疗策略,可增强MM细胞与免疫效应细胞(如T细胞和自然杀伤细胞)之间的相互作用。通过bsAbs构建免疫突触,可以促进MM细胞的清除。迄今为止,bsAbs在临床前研究中已显示出令人鼓舞的结果,评估bsAbs治疗MM患者的临床试验正在进行中。早期临床数据显示bsAbs在复发/难治性MM中具有有前景的疗效。与嵌合抗原受体修饰(CAR)-T细胞一起,bsAbs代表了精准医学的一个新维度。在本综述中,我们概述了bsAbs在MM中的原理、当前临床进展、耐药机制和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76f/7408718/abc5893eaffa/jcm-09-02166-g001.jpg

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