A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment: Simultaneous blocking of VEGF receptor-1 and 2

Feng Jen Tseng, Yu Cheng Chen, Yu Ling Lin, Nu Man Tsai, Ru Ping Lee, Yo Shong Chung, Chia Hung Chen, Yen Ku Liu, Yu Shan Huang, Chia Hsiang Hwang, Yiu Kay Lai, Kuang-Wen Liao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalCancer Biology and Therapy
Volume10
Issue number9
DOIs
StatePublished - 1 Nov 2010

Keywords

  • ADCC
  • Angiogenesis
  • Antibody dependent cellular cytotoxicity
  • Ig
  • Immunoglobulin
  • RBDV
  • Receptor-binding domain of VEGF
  • VEGF
  • Vascular endothelial growth factor

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