Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis

Abstract

Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.

Keywords:

• TTAC-0001
• VEGF signaling
• fully human neutralizing antibody, angiogenesis inhibitor
• tumor growth inhibition
• pharmacokinetics
• glioblastoma
• colorectal cancer

Disclosure of Potential Conflicts of Interest

D-H N is an adviser and stockholder of PharmAbcine.

Acknowledgments

We thank members of PharmAbcine (J-S Y, Dr. SK, Dr. WL, SS, and JY) for their contributions to scientific discussion and manuscript preparation.

Funding

This research was supported by a grant from the Korea Drug Development Fund (KDDF), funded by Ministry of Science, ICT and Future Planning, Ministry of Trade, Industry & Energy and Ministry of Health &Welfare (Grant No. KDDF-201210–14, Republic of Korea).

Supplemental Material

Supplemental data for this article can be accessed on the publisher's website