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

Sang Hyun Lee, In Cheul Jeung, Tae Woo Park, Kyungmin Lee, Dong Gwang Lee, Young Lai Cho, Tae Sup Lee, Hee Jun Na, Young Jun Park, Hee Gu Lee, Mun Sik Jeong, Kwang Hee Bae, Sang Chul Lee, Hyo Jin Lee, Young Guen Kwon, Hyo Jeong Hong, Jang Seong Kim, Jeong Ki Min

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7182-7194
Number of pages13
JournalOncotarget
Volume6
Issue number9
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Lee, S. H., Jeung, I. C., Park, T. W., Lee, K., Lee, D. G., Cho, Y. L., Lee, T. S., Na, H. J., Park, Y. J., Lee, H. G., Jeong, M. S., Bae, K. H., Lee, S. C., Lee, H. J., Kwon, Y. G., Hong, H. J., Kim, J. S., & Min, J. K. (2015). 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. Oncotarget, 6(9), 7182-7194. https://doi.org/10.18632/oncotarget.3121