[Development and prospects of bispecific antibodies for multiple myeloma].

Junichiro Yuda
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引用次数: 0

Abstract

Patients with triple-class refractory multiple myeloma once had a poor prognosis, but recently developed bispecific antibodies (bsAbs) targeting B-cell maturation antigen (BCMA), G protein-coupled receptor 5D (GPRC5D), and Fc receptor-homolog 5 (FcRH5) have shown significant clinical activity in these patients. However, responses to bsAbs are not universal, and resistance often develops during therapy. Mechanisms that mediate resistance may be tumor-intrinsic or immune-dependent. Tumor-intrinsic factors include antigen loss (biallelic or functional) due to deletion or mutation of target genes, increased soluble BCMA (for BCMA targeting bsAbs), high tumor burden, and extramedullary disease. Immune-mediated resistance highly depends on T cell fitness and the resistant immune environment. This article describes bispecific antibodies against multiple myeloma that are currently being developed.

[多发性骨髓瘤双特异性抗体的发展与前景]。
三类难治性多发性骨髓瘤患者的预后曾一度很差,但最近开发的针对B细胞成熟抗原(BCMA)、G蛋白偶联受体5D(GPRC5D)和Fc受体同源体5(FcRH5)的双特异性抗体(bsAbs)在这些患者中显示出了显著的临床活性。然而,对 bsAbs 的反应并不普遍,在治疗过程中往往会出现耐药性。产生耐药性的机制可能是肿瘤内在的,也可能是免疫依赖的。肿瘤内在因素包括靶基因缺失或突变导致的抗原缺失(双拷贝或功能性)、可溶性 BCMA 增加(针对 BCMA 靶向 bsAbs)、高肿瘤负荷和髓外疾病。免疫介导的抗药性在很大程度上取决于 T 细胞的适应性和抗药性免疫环境。本文介绍了目前正在开发的针对多发性骨髓瘤的双特异性抗体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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