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开发一种针对BCMA和PDL1的双特异IgG1抗体

Irene Cattaneo¹, Sylvie Choblet², Rut Valgardsdottir¹

¹Division of Hematology, Center of Cellular Therapy "G. Lanzani", Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, 24122 Bergamo, Italy.

Antibodies (Basel, Switzerland)

|February 23, 2024

概括

一种针对BCMA和PDL1的新型双特异性抗体有效地杀死多发性髓瘤细胞. 这种抗体表现出强烈的体外活性,支持癌症治疗的进一步发展.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

多重髓瘤 (MM) 细胞表达B细胞成熟抗原 (BCMA).
在MM中的瘤微环境表达了免疫检查点抑制剂PDL1.
双特异性抗体 (bsAbs) 提供了一种策略,可以同时针对多个抗原.

研究的目的:

设计,生产和表征一种针对BCMA和PDL1.1的新型双特异抗体 (bsAb).
评估BCMA×PDL1 bsAb.Ab的体外结合,功能活性和细胞毒性潜力.

主要方法:

在体外表征包括免疫类型和表面等离子体共振 (SPR) 结合亲和力.
功能性试验用于评估抗原阻断,补剂依赖性细胞毒性 (CDC) 和抗体依赖性细胞介导性细胞毒性 (ADCC).
在体外杀死试验中,使用外周血液单核细胞 (PBMC) 作为对抗多发性骨髓瘤细胞系的效应细胞.

主要成果:

BCMA×PDL1 bsAb 证明了对BCMA和PDL1具有纳米分子亲和力的特定和同时结合.
该bsAb有效地阻断了抗原标,并表现出功能性的Fc介导效应器功能 (CDC和ADCC).
在生理学上相关的度下,bsAb在体外诱导了目标多发性髓瘤细胞系的显著杀死.

结论:

新的BCMA×PDL1双特异性抗体得到了充分的特征,并且在多发性骨髓瘤中显示出强大的体外疗效.
bsAb能够参与BCMA和PDL1,加上Fc介导的效应器功能,支持其作为治疗剂的潜力.
这些发现为未来优化和对这种有前途的双特异抗体进行体内研究提供了坚实的基础.

关键词:

这就是为什么BCMABCMABCMA.在 PDL1 中,PDL1 是 PDL1.两种特定抗体的抗体.检查点抑制剂检查点抑制剂多发性骨髓瘤是多发性骨髓瘤的一种.

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