Mirzaei Roya, Azimi Mohammadreza, Karimi Soroush, Karimi Mahshid Seyed, Aghel Seyed Ali Mir, Salehi Malihe, Jalili Neda, Yadegari Fatemeh, Farahmand Leila
Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Invest New Drugs. 2025 May 30. doi: 10.1007/s10637-025-01546-3.
Our study aims to target Met and EpCAM to inhibit angiogenesis in breast cancer, particularly triple-negative breast cancer (TNBC). We have developed a new bispecific antibody that targets both MET and EpCAM, which are commonly overexpressed in tumor cells. This antibody aims to reduce tumor cell proliferation and spread. After cloning and expressing the anti-Met/EPCAM sequence in Escherichia coli, we confirmed its accuracy through Western blot analysis. Flow cytometry indicated its binding activities to MET and EPCAM on MDA-MB-231 and MCF-7 cell lines. Our antibody showed anti-proliferative potential as indicated by apoptosis and MTT assay, leading to the inhibition of migration and invasion in breast cancer cell lines. After conducting a thorough analysis of cytokine production, we discovered that our bispecific antibody effectively influenced the levels of IL-8 and IL-6. These cytokines play crucial roles in angiogenesis and the progression of breast cancer. These findings indicate that our bispecific antibody holds promise as a potential therapy for triple-negative breast cancer. It has the potential to impede the formation of new blood vessels in tumors, thus restraining their growth and spread.
我们的研究旨在靶向间质表皮转化因子（Met）和上皮细胞黏附分子（EpCAM）以抑制乳腺癌，尤其是三阴性乳腺癌（TNBC）中的血管生成。我们已经开发出一种靶向Met和EpCAM的新型双特异性抗体，这两种蛋白在肿瘤细胞中通常过表达。这种抗体旨在减少肿瘤细胞的增殖和扩散。在大肠杆菌中克隆并表达抗Met/EpCAM序列后，我们通过蛋白质免疫印迹分析确认了其准确性。流式细胞术表明其对MDA-MB-231和MCF-7细胞系上的Met和EpCAM具有结合活性。我们的抗体通过细胞凋亡和MTT测定显示出抗增殖潜力，从而抑制乳腺癌细胞系的迁移和侵袭。在对细胞因子产生进行全面分析后，我们发现我们的双特异性抗体有效地影响了白细胞介素-8（IL-8）和白细胞介素-6（IL-6）的水平。这些细胞因子在血管生成和乳腺癌进展中起关键作用。这些发现表明，我们的双特异性抗体有望成为三阴性乳腺癌的潜在治疗方法。它有可能阻碍肿瘤中新血管的形成，从而抑制其生长和扩散。
