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新型CDH6-向抗体-药物结合物CUSP06在多种CDH6-表达的人类癌症模型中显示出抗瘤效果

Wei Lu¹, Jing Shi², Wentao Zhang¹

¹OnCusp Therapeutics, 433 Broadway, New York, NY 10013, USA.

|August 28, 2025

概括

一种新型抗体-药物结合物CUSP06在各种癌症中向Cadherin-6 (CDH6). 临床前研究表明,CUSP06有效地杀死CDH6阳性癌细胞,具有良好的安全性,突出其治疗潜力.

科学领域:

癌症学
分子生物学
药理学

背景情况:

卡德林-6 (CDH6) 在胚胎脏发育中至关重要,但在成年组织中表达最小.
在卵巢,脏和其他癌症中,CDH6的过度表达使其成为有前途的治疗点.
CDH6在正常组织中的有限表达和瘤的过度表达促进了针对性抗体与药物联合体 (ADC) 的产生.

研究的目的:

开发和描述一种新的CDH6向ADC,CUSP06.
评估CUSP06的体外和体外疗效和安全性.

主要方法:

开发一种具有人性化的抗CDH6抗体的ADCC,一种可切割蛋白酶的链接剂,以及一种可切割蛋白酶的有效载荷 (DAR 8).
在体外评估CUSP06结合,内化,诱导DNA损伤,亡,抗增殖活性和旁观者效应.
在卵巢,脏,子宫癌和胆管癌的CDX和PDX模型中对CUSP06的抗瘤疗效进行了体内评估.
在老鼠和子中进行符合GLP的毒理研究.

主要成果:

选择性地向并内化到CDH6阳性癌细胞,诱导DNA损伤和亡.
在实验室中,CUSP06表现出强大的抗增殖和杀死旁观者的效果.
在各种CDH6阳性癌症模型 (卵巢,脏,子宫,胆管癌) 中观察到显著的抗瘤疗效.
在临床前毒理学研究中确定了良好的安全性.

结论:

对于多种CDH6阳性人类癌症,CUSP06具有强烈的临床前疗效.
这些数据支持CUSP06在治疗CDH6表达性恶性瘤方面的治疗潜力.
对于CDH6阳性癌症来说,CUSP06是一个有前途的向治疗.

关键词:

抗体与药物结合物 (ADC)CDH6 其他甲基素卡德林-6 胆管癌胆管癌其他药物卵巢癌其他宫内癌症

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