Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage.
Two vascular growth factor families, VEGF and the angiopoietins, play critical and coordinate roles in tumor progression and metastasis. A single inhibitor targeting both VEGF and angiopoietins is not available. Here, we developed a chimeric decoy receptor, namely double anti-angiogenic protein (DAAP), which can simultaneously bind VEGF-A and angiopoietins, blocking their actions. Compared to VEGF-Trap or Tie2-Fc, which block either VEGF-A or angiopoietins alone, we believe DAAP is a highly effective molecule for regressing tumor angiogenesis and metastasis in implanted and spontaneous solid tumors; it can also effectively reduce ascites formation and vascular leakage in an ovarian carcinoma model. Thus, simultaneous blockade of VEGF-A and angiopoietins with DAAP is an effective therapeutic strategy for blocking tumor angiogenesis, metastasis, and vascular leakage.
Koh
Young Jun
YJ
Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Kim
Hak-Zoo
HZ
Hwang
Seong-Ik
SI
Lee
Jeung Eun
JE
Oh
Nuri
N
Jung
Keehoon
K
Kim
Minah
M
Kim
Kyung Eun
KE
Kim
Homin
H
Lim
Nam-Kyu
NK
Jeon
Choon-Ju
CJ
Lee
Gyun Min
GM
Jeon
Byeong Hwa
BH
Nam
Do-Hyun
DH
Sung
Hoon Ki
HK
Nagy
Andras
A
Yoo
Ook Joon
OJ
Koh
Gou Young
GY
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D042682:Angiopoietins / Q000037:antagonists & inhibitors*; D000818:Animals; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D042682:Angiopoietins; D042461:Vascular Endothelial Growth Factor A