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

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dc.contributor.authorSang Hyun Lee-
dc.contributor.authorI C Jeung-
dc.contributor.authorT W Park-
dc.contributor.authorKungmin Lee-
dc.contributor.authorDong Gwang Lee-
dc.contributor.authorY L Cho-
dc.contributor.authorT S Lee-
dc.contributor.authorH J Na-
dc.contributor.authorYoung-Jun Park-
dc.contributor.authorHee Gu Lee-
dc.contributor.authorM S Jeong-
dc.contributor.authorKwang-Hee Bae-
dc.contributor.authorSang Chul Lee-
dc.contributor.authorH J Lee-
dc.contributor.authorY G Kwon-
dc.contributor.authorH J Hong-
dc.contributor.authorJang Seong Kim-
dc.contributor.authorJeong Ki Min-
dc.date.accessioned2017-04-19T10:03:26Z-
dc.date.available2017-04-19T10:03:26Z-
dc.date.issued2015-
dc.identifier.issn1949-2553-
dc.identifier.uri10.18632/oncotarget.3121ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12574-
dc.description.abstractEndostatin 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.-
dc.publisherImpact Journalsko
dc.titleExtension 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-
dc.title.alternativeExtension 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-
dc.typeArticle-
dc.citation.titleOncotarget-
dc.citation.number9-
dc.citation.endPage7194-
dc.citation.startPage7182-
dc.citation.volume6-
dc.contributor.affiliatedAuthorSang Hyun Lee-
dc.contributor.affiliatedAuthorKungmin Lee-
dc.contributor.affiliatedAuthorDong Gwang Lee-
dc.contributor.affiliatedAuthorYoung-Jun Park-
dc.contributor.affiliatedAuthorHee Gu Lee-
dc.contributor.affiliatedAuthorKwang-Hee Bae-
dc.contributor.affiliatedAuthorSang Chul Lee-
dc.contributor.affiliatedAuthorJang Seong Kim-
dc.contributor.affiliatedAuthorJeong Ki Min-
dc.contributor.alternativeName이상현-
dc.contributor.alternativeName정인철-
dc.contributor.alternativeName박태우-
dc.contributor.alternativeName이경민-
dc.contributor.alternativeName이동광-
dc.contributor.alternativeName조영래-
dc.contributor.alternativeName이태섭-
dc.contributor.alternativeName나희준-
dc.contributor.alternativeName박영준-
dc.contributor.alternativeName이희구-
dc.contributor.alternativeName정문식-
dc.contributor.alternativeName배광희-
dc.contributor.alternativeName이상철-
dc.contributor.alternativeName이효진-
dc.contributor.alternativeName권영근-
dc.contributor.alternativeName홍효정-
dc.contributor.alternativeName김장성-
dc.contributor.alternativeName민정기-
dc.identifier.bibliographicCitationOncotarget, vol. 6, no. 9, pp. 7182-7194-
dc.identifier.doi10.18632/oncotarget.3121-
dc.subject.keywordAngiogenesis inhibitors-
dc.subject.keywordColorectal carcinoma-
dc.subject.keywordEndostatin-
dc.subject.keywordTumor-associated glycoprotein-72-
dc.subject.keywordVascular endothelial growth factor-
dc.subject.localangiogenesis inhibitor-
dc.subject.localAngiogenesis inhibitors-
dc.subject.localangiogenesis inhibitors-
dc.subject.localAngiogenesis inhibitor-
dc.subject.localColorectal carcinoma-
dc.subject.localcolorectal carcinoma-
dc.subject.localEndostatin-
dc.subject.localTumor-associated glycoprotein-72-
dc.subject.localvascular endothelial growth factor-
dc.subject.localVascular endothelial growth factor (VEGF)-
dc.subject.localvascular endothelial growth factor (VEGF)-
dc.subject.localVascular endothelial growth factor-
dc.description.journalClassN-
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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