文章：

靶向肿瘤选择性HER2表位的mAb104抗体-药物偶联物特性研究

Characterisation of mAb104 Antibody–Drug Conjugates Targeting a Tumour-Selective HER2 Epitope

原文发布日期：13 September 2025

DOI: 10.3390/cancers17182995

类型: Article

开放获取: 是

英文摘要：

Background: The novel anti-HER2 antibody 104 (mAb104) targets a unique tumour-specific epitope, lacks normal tissue binding and can internalise into tumour cells, thus supporting its development into antibody drug conjugates (ADCs). Methods: We now describe the binding properties and preclinical activity of mAb104-ADCs developed through the conjugation of mAb104 via linkers to the anti-microtubule drug maytansoinoid ematansine (DM1-SMCC; DM1), topoisomerase I inhibitor, exatecan derivative (MC-GGFG-DX8951; DX8951) or microtubule disruptor monomethyl auristatin E (MC-vc-PAB-MMAE; MMAE). Results: Mab104-ADCs demonstrate dose-dependent cytotoxicity in vitro. The safety of single-dose mAb104-DX8951 was demonstrated in vivo at doses up to 10 mg/kg. MAb104-ADCs also demonstrated potent and prolonged anti-tumour activity in a range of tumour types with variable HER2 expression. Mab104-DX8951 showed significant responses in trastuzumab-resistant HER2-positive breast cancer, low HER2-expressing cancers, as well as HER2-overexpressing cancers. Conclusion: These findings indicate the potential for tumour-specific targeting of HER2-expressing tumours with mAb104-ADCs.

摘要翻译： 

背景：新型抗HER2抗体104（mAb104）靶向独特的肿瘤特异性表位，不结合正常组织，并能内化至肿瘤细胞内，这些特性支持其开发为抗体药物偶联物（ADC）。方法：本研究通过将mAb104与抗微管药物美坦辛衍生物DM1（DM1-SMCC；DM1）、拓扑异构酶I抑制剂依沙替康衍生物（MC-GGFG-DX8951；DX8951）或微管破坏剂单甲基奥瑞他汀E（MC-vc-PAB-MMAE；MMAE）经连接子偶联，系统阐述mAb104-ADC的结合特性与临床前活性。结果：MAb104-ADC在体外呈现剂量依赖性细胞毒性。单剂量mAb104-DX8951在高达10 mg/kg的剂量下于体内验证了安全性。在不同HER2表达水平的多种肿瘤模型中，mAb104-ADC均表现出强效且持久的抗肿瘤活性。MAb104-DX8951在曲妥珠单抗耐药的HER2阳性乳腺癌、低HER2表达癌症以及HER2过表达癌症中均显示出显著疗效。结论：这些发现表明mAb104-ADC具有靶向HER2表达肿瘤的潜在特异性治疗价值。

原文链接：

Characterisation of mAb104 Antibody–Drug Conjugates Targeting a Tumour-Selective HER2 Epitope