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CEA-4-1BBL:CEACAM5-向的4-1BB干融合蛋白,用于与CEA-TCB的Cis共刺激

Christina Claus¹, Claudia Ferrara-Koller¹, Johannes Sam¹

¹Roche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Wagistrasse 10, 8952 Schlieren, Switzerland.

Antibodies (Basel, Switzerland)

|November 24, 2025

概括

将T细胞双特异性抗体 (TCB) 与CEACAM5向的4-1BBL融合蛋白结合起来,需要仔细选择CEACAM5表位因子,以获得最佳的T细胞活性. 在体内,T84.66-LCHA-4-1BBL融合蛋白显示出优异的抗瘤疗效,使其成为CEA-TCB的首选合作伙伴.

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:

双特异性T细胞抗体 (TCBs) 激活T细胞受体信号传递,用于瘤抗原的识别.
同刺激信号2对于增强和维持TCB活动至关重要.
针对CEACAM5的4-1BBL抗体融合蛋白正在研究与CEA-TCB (cibisatamab,RG7802) 的组合.

研究的目的:

在与CEA-TCB结合时,研究CEACAM5表位和T细胞活性之间的关系.
为了确定最佳的CEACAM5向的4-1BBL抗体融合蛋白,用于组合疗法.
评估不同CEACAM5-4-1BBL融合蛋白与CEA-TCB结合的体内疗效.

主要方法:

使用Jurkat-4-1BB报告者和PBMC测定,生成CEACAM5向的双特异性4-1BBL抗体融合蛋白 (CEA-4-1BBLs) 和体外表征.
评估棚CEA对体外活性和cynomolgus交叉反应性的影响.
在人类干细胞人性化NSG小鼠异种移植模型 (MKN-45和HPAFII瘤) 中体内疗效的评估.

主要成果:

在报告者和初级T细胞测定中,MFE23-4-1BBL和Sm9b-4-1BBL与CD3抗体V9表现出优异的活性.
当与CEA-TCB结合时,T84.66-LCHA-4-1BBL和A5B7-4-1BBL的性能更好.
T84.66-LCHA-4-1BBL在人性化的NSG小鼠异种移植模型中显示出最好的抗瘤疗效.

结论:

实验室试验不足以充分评估CEA-TCB与CEA-4-1BBL融合蛋白结合的疗效.
使用多种细胞检测和体内疗效研究进行查对于候选人选择至关重要.
根据T84.66-LCHA-4-1BBL.BBL的综合数据,T84.66-LCHA被选为CEA-TCB的最佳组合合作伙伴.

关键词:

在 4-1BBBB 中.在CD137中,CD137中,CD137中,CD137中在 CEACAM5 中.在TNFRSF9中.标志性标志性标志性标志性膜 - 远端膜 - 远端膜 - 靠近的边缘

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