RGD Reference Report - TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis. - Rat Genome Database

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

Authors: Lee, Weon Sup  Pyun, Bo-Jeong  Kim, Sung-Woo  Shim, Sang Ryeol  Nam, Ju Ryoung  Yoo, Ji Young  Jin, Younggeon  Jin, Juyoun  Kwon, Young-Guen  Yun, Chae-Ok  Nam, Do-Hyun  Oh, Keunhee  Lee, Dong-Sup  Lee, Sang Hoon  Yoo, Jin-San 
Citation: Lee WS, etal., MAbs. 2015;7(5):957-68. doi: 10.1080/19420862.2015.1045168. Epub 2015 May 5.
RGD ID: 126925211
Pubmed: PMID:25942475   (View Abstract at PubMed)
PMCID: PMC4622656   (View Article at PubMed Central)
DOI: DOI:10.1080/19420862.2015.1045168   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endothelial tube morphogenesis  IMP 126925211 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)


Additional Information