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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
- Source :
- mAbs
- Publication Year :
- 2015
- Publisher :
- Taylor & Francis, 2015.
-
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.
- Subjects :
- Angiogenesis
Immunology
TTAC-0001
Mice, Nude
colorectal cancer
Antineoplastic Agents
Apoptosis
Pharmacology
Biology
Antibodies, Monoclonal, Humanized
Metastasis
chemistry.chemical_compound
In vivo
Report
Cell Line, Tumor
Neoplasms
medicine
tumor growth inhibition
Immunology and Allergy
Animals
Humans
Receptor
Mice, Inbred BALB C
Neovascularization, Pathologic
glioblastoma
Antibodies, Monoclonal
Kinase insert domain receptor
VEGF signaling
medicine.disease
HCT116 Cells
Vascular Endothelial Growth Factor Receptor-2
Xenograft Model Antitumor Assays
Tumor Burden
Vascular endothelial growth factor
Treatment Outcome
chemistry
Area Under Curve
Cancer cell
fully human neutralizing antibody, angiogenesis inhibitor
MCF-7 Cells
Signal transduction
Colorectal Neoplasms
pharmacokinetics
HT29 Cells
Subjects
Details
- Language :
- English
- ISSN :
- 19420870 and 19420862
- Volume :
- 7
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- mAbs
- Accession number :
- edsair.doi.dedup.....371574904a09f88c629ba6c1579d30ff