Suppr超能文献

IBI379,一种新型的 B 细胞成熟抗原/CD3 双特异性 T 细胞衔接子,在多发性骨髓瘤的多个临床前模型中显示出高抗肿瘤疗效。

IBI379, a novel B cell maturation antigen/CD3 bispecific T-cell engager, displays high antitumor efficacy in preclinical models of multiple myeloma.

机构信息

College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China; Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, 215123, Jiang Su, China.

Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, 215123, Jiang Su, China.

出版信息

Cancer Lett. 2022 Jun 28;536:215663. doi: 10.1016/j.canlet.2022.215663. Epub 2022 Apr 4.

Abstract

Multiple myeloma (MM) is a hematological malignancy that results from the malignant proliferation of plasma cells in the bone marrow. B cell maturation antigen (BCMA) is highly selectively expressed in malignant plasma cells and is a novel therapeutic target for MM. Here, we developed a bispecific T cell engager, IBI379, that targets BCMA and CD3, and investigated its antitumor efficacy against MM. IBI379 showed strong binding affinity with both BCMA and CD3, which triggered T cell activation, proliferation, and cytokine release. An in vitro study demonstrated that IBI379 induced the lysis of MM cells expressing differing levels of BCMA on the cell surface. Administration of IBI379 in H929 or Daudi-BCMA cell xenograft mouse models significantly inhibited tumor growth without inducing body weight loss. The mechanism of action study revealed the accumulation of CD4CD8 T cells and granzyme B-positive T cells in tumors that were treated with IBI379. Moreover, administration of low dose of IBI379 in cynomolgus monkeys was well-tolerated and induced the depletion of BCMA B cells and a mild transient increase of cytokines. Collectively, these results demonstrate that IBI379 is a highly potent therapeutic strategy for depleting BCMA-positive B cells and is a promising approach for the treatment of MM.

摘要

多发性骨髓瘤(MM)是一种血液系统恶性肿瘤,源于骨髓中浆细胞的恶性增殖。B 细胞成熟抗原(BCMA)在恶性浆细胞中高度选择性表达,是 MM 的一种新型治疗靶点。在这里,我们开发了一种针对 BCMA 和 CD3 的双特异性 T 细胞衔接子 IBI379,并研究了其针对 MM 的抗肿瘤疗效。IBI379 与 BCMA 和 CD3 均表现出很强的结合亲和力,从而触发 T 细胞激活、增殖和细胞因子释放。体外研究表明,IBI379 可诱导表达不同水平 BCMA 的 MM 细胞裂解。在 H929 或 Daudi-BCMA 细胞异种移植小鼠模型中给予 IBI379 可显著抑制肿瘤生长,而不引起体重减轻。作用机制研究显示,在接受 IBI379 治疗的肿瘤中,CD4CD8 T 细胞和颗粒酶 B 阳性 T 细胞积聚。此外,在食蟹猴中给予低剂量的 IBI379 耐受性良好,并诱导 BCMA B 细胞耗竭和细胞因子轻度短暂增加。总之,这些结果表明 IBI379 是一种高效的治疗策略,可用于耗竭 BCMA 阳性 B 细胞,是治疗 MM 的一种有前途的方法。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验