期刊
MABS
卷 7, 期 6, 页码 1195-1204出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2015.1086854
关键词
TTAC-0001; VEGF signaling; fully human neutralizing antibody; angiogenesis inhibitor; tumor growth inhibition; pharmacokinetics; glioblastoma; colorectal cancer
资金
- Korea Drug Development Fund (KDDF) - Ministry of Science, ICT and Future Planning, Ministry of Trade, Industry & Energy and Ministry of Health & Welfare, Republic of Korea [KDDF-201210-14]
- National Research Foundation of Korea [KDDF-201210-14] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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