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针对分子放射治疗的CD44v6向抗体的亲和力成熟和优化

Anja Charlotte Lundgren Mortensen¹, Camilla Hofström², Helena Persson²

¹Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Uppsala University, Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala, Sweden.

Nuclear medicine and biology

|April 20, 2025

概括

研究人员优化了针对分子放射治疗的CD44v6向抗体,提高了瘤保留率,并可能提高安全性. 主要候选者UU-A-155显示出临床应用的前景.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
放射性药物放射性药物放射性药物

背景情况:

CD44v6抗原是癌症治疗的目标.
基于抗体的分子放射治疗为癌症治疗提供了一种有针对性的方法.
优化抗体亲和力和效应器功能对于治疗疗效至关重要.

研究的目的:

为了提高针对CD44v6的抗体UU-40的疗效,用于分子放射治疗.
通过亲和力成熟和IgG子类优化来改善抗体亲和力,瘤保留和安全概况.

主要方法:

在人类IgG4和IgG1 (LALA突变) 格式中生成和表征亲和力成熟的抗体变体.
表面等离子体共振和LigandTracer测试用于亲和度和异常率的确定.
在异种移植模型中使用标记为卢-177 (Lu) 的抗体进行了体内生物分布研究.
Fcγ受体结合测定和物种交叉反应性研究.

主要成果:

与父母的UU-40相比,一些亲和力成熟的候选人表现出更高的亲和力和异常率.
选择的177个标记为Lu的抗体证明了瘤保留的改善,而UU-A-155显示了性能.
IgG1 LALA格式显示Fcγ受体结合减少,这表明安全性状况有所改善.
UU-A-155 已证实与 cynomolgus 和子v6的结合.

结论:

亲和力成熟和IgG子类优化显著改善了针对CD44v6的抗体的性能.
UU-A-155 是分子放射治疗中临床转化的一个有希望的领先候选人.
全面的体外和体内评估对于开发有效的基于抗体的癌症疗法至关重要.

关键词:

抗体成熟的时间在CD44v6中,在地图上绘制出地图的地图.在Fcγ-silencing中使用.在 IgG1 中,LALA 分子辐射疗法分子辐射疗法

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