Fusion Protein HSA/TIMP-2 Effectively Inhibits Prostate Tumor Growth through Anti-Angiogenesis

Author

DR SANG MOK LEE
Hannam University Daedok Valley Campus
461-71, Jeonmin-Dong, Yuseong-ku
Daejon-city, 305-811, Korea
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Language

English

Title

Fusion Protein HSA/TIMP-2 Effectively Inhibits Prostate Tumor Growth through Anti-Angiogenesis

Proceeding

7th INTRACOM – 2nd ICBWI 2009

Date

23rd-26th July 2009

Place Held

PWTC, Kuala Lumpur

Abstract

Timp-2 is a natural inhibitor of the matrix metalloproteinases (MMPs), especially MMP-2 and has been studied for an attractive cancer therapeutic candidate. However, therapeutic application of TIMP-2 protein has been limited by its low yield production of the bioactive form. Here, using high level production of TIMP-2 fusion protein with human serum albumin (HAS/TIMP-2) in the yeast Saccharomyces cerevisiae, we investigated pharmacokinetic and pharmacodynamic properties and further evaluated in vivo efficacy of the HAS/TIMP-2 in the prostate cancer animal model. Fluorescent optical imaging with Cy5.5 conjugated HAS/TIMP-2 showed pro-long half life circulations in blood and clearly high accumulation in the tumor. In the tumor mouse model harboring MLL prostate cancer cell expressing luciferase, systemic treatment of HSA/TIMP-2 significant inhibited tumor growth through retardation of tumor angiogenesis. Furthermore, enhanced anti-tumor responses were measured with combinational chemotherapy with Paclitaxel or 5-FU. These results suggested that HAS/TIMP-2 therapeutic potential in the prostate cancer is clearly promising.

Keywords

Fusion Protein HAS/TIMP-2, Prostate tumor, Anti-Angiogenesis

Session

Plenary 9

Topic

Not Available