Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor
Xian-wen Hu, Hai-feng Duan, Hai-feng Duan, Shu-yuan Pan, Yong-mei Li, Yongyi Xi, Su-Rong Zhao, Liang Yin, Jin-feng Li, Hui-Peng Chen and Chu-Tse Wu
volume 7 | issue 5
May 2008Pages: 651 - 659
Subscribe to this journal for $129/year
Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. In this study, ATF-Fc, an antibody-like molecule comprising the amino-terminal fragment of human uPA (ATF) linked to the Fc fragment of human IgG1 via a flexible linker was developed. Its antitumor activities were evaluated in vitro and in vivo. The results showed that ATF-Fc had obvious cytotoxic effect on several types of tumor cells, which is dependent on cellular expression of uPAR and its Fc fragment. Treatment with ATF-Fc caused a significant suppression on tumor growth and metastasis of xenograft human tumors (MCF-7 breast cancer and BGC-823 gastric cancer) in athymic nude mice. Furthermore, we demonstrated that ATF-Fc had an anti-angiogenesis activity both in vitro and in vivo. In conclusion, we provided a novel therapeutic antibody-like molecule in the management of a variety of solid tumors by disrupting the uPA/uPAR interaction.