TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis

Weon Sup Lee, Bo Jeong Pyun, Sung Woo Kim, Sang Ryeol Shim, Ju Ryoung Nam, Ji Young Yoo, Younggeon Jin, Juyoun Jin, Young-Guen Kwon, Chae Ok Yun, Do Hyun Nam, Keunhee Oh, Dong Sup Lee, Sang Hoon Lee, Jin San Yoo

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12 Citations (Scopus)

Abstract

Angiogenesis is one of the most important processes for cancer cell survival, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its receptor, particularly VEGF receptor-2 (VEGFR-2, or kinase insert domain-containing receptor, KDR), play critical roles in tumor-associated angiogenesis. We developed TTAC-0001, a human monoclonal antibody against VEGFR-2/KDR from a fully human naïve single-chain variable fragment phage library. TTAC-0001 was selected as a lead candidate based on its affinity, ligand binding inhibition and inhibition of VEGFR-2 signal in human umbilical vein endothelial cells (HUVEC). TTAC-0001 inhibited binding of VEGF-C and VEGF-D to VEGFR-2 in addition to VEGF-A. It binds on the N-terminal regions of domain 2 and domain 3 of VEGFR-2. It could inhibit the phosphorylation of VEGFR-2/KDR and ERK induced by VEGF in HUVEC. TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings and neovascularization in mouse matrigel model in vivo. Our data indicates that TTAC-0001 blocks the binding of VEGFs to VEGFR-2/KDR and inhibits VEGFR-induced signaling pathways and angiogenesis. Therefore, these data strongly support the further development of TTAC-0001 as an anti-cancer agent in the clinic.

Original languageEnglish
Pages (from-to)957-968
Number of pages12
JournalmAbs
Volume7
Issue number5
DOIs
Publication statusPublished - 2015 Jan 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Lee, W. S., Pyun, B. J., Kim, S. W., Shim, S. R., Nam, J. R., Yoo, J. Y., Jin, Y., Jin, J., Kwon, Y-G., Yun, C. O., Nam, D. H., Oh, K., Lee, D. S., Lee, S. H., & Yoo, J. S. (2015). TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis. mAbs, 7(5), 957-968. https://doi.org/10.1080/19420862.2015.1045168