A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells

双特异性 IGF-I/II 人类工程抗体结构域可抑制乳腺癌细胞中的 IGF 信号传导

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作者:Zhizhen Chen, Jie Liu, Dafeng Chu, Yaming Shan, Guixing Ma, Hongmin Zhang, Xiaohua Douglas Zhang, Pu Wang, Qiang Chen, Chuxia Deng, Weizao Chen, Dimiter S Dimitrov, Qi Zhao

Abstract

The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II. It also significantly inhibited the growth of breast cancer cells. Therefore, the anti-IGF-I/II eAd offers an alternative approach to target both the IGF-1R signaling pathways through the inhibition of IGF-I/II.

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