CD44v9作为在晚期乳腺癌中抗体-药物结合物的治疗标

CD44v9作为在晚期乳腺癌中抗体-药物结合物的治疗标

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Updated: Feb 19, 2026

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Dileep R Reddy¹, McKenna E Flynn², Yasuaki Anami³

¹Preclinical Core, University of Hawai'i Cancer Center, Honolulu, HI, USA; Cancer Biology Program, University of Hawai'i Cancer Center, Honolulu, HI, USA.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|February 17, 2026

概括

研究人员确定了CD44变异异型9 (CD44v9) 作为乳腺癌中抗体-药物合物 (ADC) 的有希望的新标. 这种新的目标即使在耐药病例中也显示出有效性,为高级疾病治疗提供了希望.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫治疗是一种免疫疗法.

背景情况:

抗体-药物合物 (ADC) 已经改变了乳腺癌的治疗方法,主要针对HER2和TROP2.
瘤异质性和耐药性限制了目前的ADC疗效,需要新的点.
CD44变体异型9 (CD44v9) 在侵袭性乳腺癌中表达高,与干性和耐药性有关.

研究的目的:

开发和评估一种针对CD44v9的新型ADC,用于乳腺癌治疗.
评估CD44v9作为克服治疗耐药性的瘤特异性标.

主要方法:

开发了一种针对CD44v9的仿真单克隆抗体,并将其与MMAF (抗CD44v9-MMAF) 结合.
通过免疫组织化学分析了乳腺癌和正常组织中的CD44v9表达.
在各种乳腺癌模型中评估了抗CD44v9-MMAF的结合,内化和体外/体内细胞毒性,包括耐药的乳腺癌模型.

主要成果:

CD44v9在乳腺癌中高度表达,但在大多数正常组织中不存在.
抗CD44v9-MMAF表现出特定的结合,高效的内化和强大的抗原依赖性细胞毒性.
在体内,ADC显示了剂量依赖的瘤抑制,系统毒性最小.
针对CD44v9的治疗在对现有ADCs (trastuzumab deruxtecan,sacituzumab govitecan,T-DM1) 耐药的模型中仍然有效.

结论:

CD44v9是晚期乳腺癌中ADC的瘤特异性和临床可行的标.
针对CD44v9的ADC为治疗耐药性疾病患者提供了潜在的治疗策略.

关键词:

晚期乳腺癌是什么晚期乳腺癌抗体 - 药物结合物,微管体抑制剂单甲基auristatin F.CD44的第九个变异.

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