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通过ISB 1442对CD38的双相结,可以增加细胞抗体密度和增强细胞活力

Jeremy Loyau¹, Thierry Monney¹, Marco Montefiori¹

¹Ichnos Glenmark Innovation, New York, NY, USA.

|January 30, 2025

概括

ISB 1442是一种新型双特异性抗体,旨在通过向CD38和CD47来治疗血液癌症. 它独特的双相基结构增强了瘤细胞的结合,并克服了多发性骨髓瘤中的免疫逃避.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
结构生物学结构生物学

背景情况:

多发性骨髓瘤等血液性恶性瘤表达CD38.
瘤细胞可以通过CD47信号来逃避免疫检测.
双特异性抗体提供有针对性的治疗策略.

研究的目的:

描述ISB 1442抗体的发现,优化和表征.
通过结构和功能分析,阐明ISB 1442的作用机制.
评估ISB 1442对CD38和CD47.7的结合特性和特异性.

主要方法:

反CD38的高分辨率共晶结构与CD38. Fabs具有CD38.
生物物理测定包括使用多角度光散射 (SEC-MALS) 和表面等离子体共振 (SPR) 的尺寸排除色谱.
细胞结合测定和电子显微镜测试以确定抗体-抗原固态度和复合物形成.

主要成果:

ISB 1442表现出对CD38的双基结合,准非重叠的表位.
该抗体与溶液中的CD38形成2:2复合体,通过SEC-MALS和电子显微镜验证.
结构和功能数据显示增强的转结合,防止 cis 结合,并增加对 CD38 的嗜好.

结论:

ISB 1442的双向型设计使得CD38在不同的受体密度上具有优越的准能力.
增强的CD38结合促进了近端CD47阻断,抵消了瘤的免疫逃逸.
ISB 1442显示出治疗CD38+血液性恶性瘤的潜力,包括多发性骨髓瘤.

关键词:

双双特异性抗体双双特异性抗体 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD47 CD47 CD47 CD47 CD47 CD47 CD47 CD47 CD47 CD47 CD47 CD47 这就是为什么CDC CDC CDC.共同晶体结构的共同晶体结构内在细胞调节器的内在细胞调节器.

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