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Title 

Extension of the in vivo half-life of endostatin and its improved anti-tumor activities upon fusion to a humanized antibody against tumor-associated glycoprotein 72 in a mouse model of human colorectal carcinoma

Authors 

Sang Hyun LeeI C JeungT W ParkKungmin LeeDong Gwang LeeY L ChoT S LeeH J NaYoung-Jun ParkHee Gu LeeM S JeongKwang-Hee BaeSang Chul LeeH J LeeY G KwonH J HongJang Seong KimJeong Ki Min

Publisher 

Impact Journals

Issue Date 

2015

Citation 

Oncotarget, vol. 6, no. 9, pp. 7182-7194

Keywords 

Angiogenesis inhibitorsColorectal carcinomaEndostatinTumor-associated glycoprotein-72Vascular endothelial growth factor

Abstract 

Endostatin is an endogenous angiogenesis inhibitor that exhibits potential anti-tumor efficacy in various preclinical animal models. However, its relatively short in vivo half-life and the long-term, frequent administration of high doses limit its widespread clinical use. In this study, we evaluated whether a fusion protein of murine endostatin (mEndo) to a humanized antibody against tumor-associated glycoprotein 72 (TAG-72), which is highly expressed in several human tumor tissues including colon cancer, can extend the serum half-life and improve the anti-tumor efficacy of endostatin by targeted delivery to the tumor mass. The fusion protein (3E8-mEndo) and mEndo showed improved anti-angiogenic activity in vitro and in vivo, predominantly by interfering with pro-angiogenic signaling triggered by vascular endothelial growth factor (VEGF). Moreover, in mice treated with 3E8-mEndo, we observed a markedly prolonged serum half-life and significantly inhibited tumor growth. The improved anti-tumor activity of 3E8-mEndo can be partially explained by increased local concentration in the tumor mass due to targeted delivery of 3E8-mEndo to implanted colon tumors. Collectively, our data clearly indicate that tumor-targeting antibody fusions to endostatin are a powerful strategy that improves the poor pharmacokinetic profile and anti-tumor efficacy of endostatin.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.3121

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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