DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jung-Eun | ko |
dc.contributor.author | Kim, Chan | ko |
dc.contributor.author | Yang, Hannah | ko |
dc.contributor.author | Park, Intae | ko |
dc.contributor.author | Oh, Nuri | ko |
dc.contributor.author | Hua, Serenus | ko |
dc.contributor.author | Jeong, Haneul | ko |
dc.contributor.author | An, Hyun Joo | ko |
dc.contributor.author | Kim, Sun Chang | ko |
dc.contributor.author | Lee, Gyun Min | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.contributor.author | Kim, Ho-Min | ko |
dc.date.accessioned | 2015-04-08T04:58:36Z | - |
dc.date.available | 2015-04-08T04:58:36Z | - |
dc.date.created | 2014-12-29 | - |
dc.date.created | 2014-12-29 | - |
dc.date.created | 2014-12-29 | - |
dc.date.issued | 2015-02 | - |
dc.identifier.citation | MOLECULAR CANCER THERAPEUTICS, v.14, no.2, pp.470 - 479 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | http://hdl.handle.net/10203/195611 | - |
dc.description.abstract | Antiangiogenic therapies targeting VEGFA have been commonly used in clinics to treat cancers over the past decade. However, their clinical efficacy has been limited, with drawbacks including acquisition of resistance and activation of compensatory pathways resulting from elevated circulating VEGFB and placental growth factor (PlGF). To bypass these disadvantages, we developed a novel glycosylated soluble decoy receptor fusion protein, VEGF-Grab, that can neutralize VEGFA, VEGFB, and PlGF. VEGF-Grab has the second and third immunoglobulin (Ig)-like domains of VEGF receptor 1 (VEGFR1) fused to IgG1 Fc, with three potential glycosylation sites introduced into the third Ig-like domain of VEGF-Grab by mutagenesis. Compared with VEGF-Trap, VEGF-Grab showed more potent decoy activity against VEGF and PlGF, mainly attributed to the VEGFR1 backbone. Most importantly, the negatively charged O-glycans attached to the third Ig-like domain of VEGFR1 counterbalanced the originally positively charged VEGFR1 backbone, minimizing nonspecific binding of VEGF-Grab to the extracellular matrix, and resulting in greatly improved pharmacokinetic profile. These advancements led to stronger and more durable antiangiogenic, antitumor, and antimetastatic efficacy in both implanted and spontaneous tumor models as compared with VEGF-Trap, while toxicity profiles were comparable with VEGF-Trap. Collectively, our results highlight VEGF-Grab as a promising therapeutic candidate for further clinical drug development. | - |
dc.language | English | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | Novel Glycosylated VEGF Decoy Receptor Fusion Protein, VEGF-Grab, Efficiently Suppresses Tumor Angiogenesis and Progression | - |
dc.type | Article | - |
dc.identifier.wosid | 000349538700015 | - |
dc.identifier.scopusid | 2-s2.0-84923329768 | - |
dc.type.rims | ART | - |
dc.citation.volume | 14 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 470 | - |
dc.citation.endingpage | 479 | - |
dc.citation.publicationname | MOLECULAR CANCER THERAPEUTICS | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-14-0968-T | - |
dc.contributor.localauthor | Kim, Sun Chang | - |
dc.contributor.localauthor | Lee, Gyun Min | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.localauthor | Kim, Ho-Min | - |
dc.contributor.nonIdAuthor | Hua, Serenus | - |
dc.contributor.nonIdAuthor | Jeong, Haneul | - |
dc.contributor.nonIdAuthor | An, Hyun Joo | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | MYELOID CELLS | - |
dc.subject.keywordPlus | TRAP | - |
dc.subject.keywordPlus | BEVACIZUMAB | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | DISEASES | - |
dc.subject.keywordPlus | ANTIBODY | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | LIGANDS | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.