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.
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.
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.|b Department of Health Sciences and Technology ; SAIHST, Sungkyunkwan University ; Seoul 06351 , Korea.
Dong Geon
DG
Kim
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.
Younggeon
Y
Jin
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.
Juyoun
J
Jin
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.|c Department of Neurosurgery ; Samsung Medical Center, Sungkyunkwan University School of Medicine ; Seoul 06351 , Korea.
Heekyoung
H
Yang
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.|b Department of Health Sciences and Technology ; SAIHST, Sungkyunkwan University ; Seoul 06351 , Korea.|d Department of Anatomy and Cell Biology ; Sungkyunkwan University School of Medicine ; Seoul 06351 , Korea.
Kyeung Min
KM
Joo
e PharmAbcine; Inc., Daejeon Bioventure Town ; Daejeon 34054 , Korea.
Weon Sup
WS
Lee
e PharmAbcine; Inc., Daejeon Bioventure Town ; Daejeon 34054 , Korea.
Sang Ryeol
SR
Shim
e PharmAbcine; Inc., Daejeon Bioventure Town ; Daejeon 34054 , Korea.
Sung-Woo
SW
Kim
e PharmAbcine; Inc., Daejeon Bioventure Town ; Daejeon 34054 , Korea.
Jinsang
J
Yoo
f Bio Division, Hanwha Chemical ; Seoul 04541 , Korea.
Sang Hoon
SH
Lee
e PharmAbcine; Inc., Daejeon Bioventure Town ; Daejeon 34054 , Korea.
Jin-San
JS
Yoo
a Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center ; Seoul 06351 , Korea.|b Department of Health Sciences and Technology ; SAIHST, Sungkyunkwan University ; Seoul 06351 , Korea.|c Department of Neurosurgery ; Samsung Medical Center, Sungkyunkwan University School of Medicine ; Seoul 06351 , Korea.
Do-Hyun
DH
Nam
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019540:Area Under Curve; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D040301:Vascular Endothelial Growth Factor Receptor-2; C570591:olinvacimab
TTAC-0001; VEGF signaling; colorectal cancer; fully human neutralizing antibody, angiogenesis inhibitor; glioblastoma; pharmacokinetics; tumor growth inhibition