Abstract
Abstract Tumor angiogenesis is the process that leads to the formation of blood vessels in a tumor and a prognostic indicator in various cancers. Vascular endothelial growth factor (VEGF) and its receptors are considered to be primary regulators of tumor-induced angiogenesis and activation of VEGFR2/KDR is the major signaling pathway for tumor growth. In addition, VEGFR2/KDR is also expressed in many cancer cells, and regulates cell growth and survival through autocrine pathway. In this study, we evaluated the therapeutic potential of TTAC-0001, fully human antibody against VEGFR2/KDR, for the inhibition of tumor growth. In the tube formation assay using HUVEC, TTAC-0001 exhibited a potent anti-angiogenic activity in vitro. In U-87 MG glioblastoma cells, TTAC-0001 significantly inhibited the phosphorylation of VEGFR2/KDR mediated by VEGF. To reveal in vivo efficacy, we have tested TTAC-0001 in glioblastoma and colorectal xenograft models. We demonstrated that antitumor activity of TTAC-0001 in preclinical models correlated with induction of growth arrest and apoptosis as well as the inhibition of angiogenesis. Currently, we are evaluating the combination of TTAC-0001 with chemotherapeutic agents in xenograft models. A single dose study performed in mouse allowed us to establish the relationship between the pharmacokinetics (PK) and efficacy of TTAC-0001. Taken together, our data suggest that targeting VEGFR2 pathway by TTAC-0001 would be a promising candidate for the treatment of cancer. (This study was supported by grants of the Korea Healthcare technology R&D Project, Ministry for Health & Welfare Affairs (A092255 and A040016) and Advanced Medi-cluster R&D Project, DaejeonTechnoPark, Republic of Korea. Seol HJ and Nam DH are co-corresponding authors for this manuscript.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 647. doi:10.1158/1538-7445.AM2011-647
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