A dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulation

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dc.contributor.authorKim, Tae Yoonko
dc.contributor.authorSeo, Hyo Deokko
dc.contributor.authorLee, Joong-jaeko
dc.contributor.authorKang, Jung Aeko
dc.contributor.authorKim, Woo Sikko
dc.contributor.authorKim, Hye-Minko
dc.contributor.authorSong, Ha-Yeonko
dc.contributor.authorPark, Ji Minko
dc.contributor.authorLee, Dong-Eunko
dc.contributor.authorKim, Hak-Sungko
dc.date.accessioned2018-07-24T02:22:09Z-
dc.date.available2018-07-24T02:22:09Z-
dc.date.created2018-07-04-
dc.date.created2018-07-04-
dc.date.created2018-07-04-
dc.date.created2018-07-04-
dc.date.created2018-07-04-
dc.date.issued2018-06-
dc.identifier.citationJOURNAL OF CONTROLLED RELEASE, v.279, pp.282 - 291-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://hdl.handle.net/10203/244014-
dc.description.abstractSmall-sized non-antibody scaffolds have attracted considerable interest as alternatives to immunoglobulin antibodies. However, their short half-life is considered a drawback in the development of therapeutic agents. Here we demonstrate that a homo-dimeric form of a repebody enhances the anti-tumor activity than a monomeric form through prolonged blood circulation. Spytag and spycatcher were genetically fused to the C-terminus of a respective human IL-6-specific repebody, and the resulting two repebody constructs were mixed at an equimolar ratio to produce a homo-dimeric form through interaction between spytag and spycatcher. The homo-dimeric repebody was detected as a single band in the SDS-PAGE analysis with an expected molecular size (78 kDa), showing high stability and homogeneity. The dimeric repebody was shown to simultaneously accommodate two hIL-6 molecules, and its binding affinity for hIL-6 was estimated to be comparable to a monomeric repebody. The serum concentration of the dimeric repebody was observed to be about 5.5 times higher than a monomeric repebody, consequently leading to considerably higher tumor suppression effect in human tumor xenograft mice. The present approach can be effectively used for prolonging the blood half-life of small-sized protein binders, resulting in enhanced therapeutic efficacy.-
dc.languageEnglish-
dc.publisherELSEVIER SCIENCE BV-
dc.titleA dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulation-
dc.typeArticle-
dc.identifier.wosid000433211300026-
dc.identifier.scopusid2-s2.0-85046160855-
dc.type.rimsART-
dc.citation.volume279-
dc.citation.beginningpage282-
dc.citation.endingpage291-
dc.citation.publicationnameJOURNAL OF CONTROLLED RELEASE-
dc.identifier.doi10.1016/j.jconrel.2018.04.039-
dc.contributor.localauthorKim, Hak-Sung-
dc.contributor.nonIdAuthorLee, Joong-jae-
dc.contributor.nonIdAuthorKang, Jung Ae-
dc.contributor.nonIdAuthorKim, Woo Sik-
dc.contributor.nonIdAuthorKim, Hye-Min-
dc.contributor.nonIdAuthorSong, Ha-Yeon-
dc.contributor.nonIdAuthorPark, Ji Min-
dc.contributor.nonIdAuthorLee, Dong-Eun-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorRepebody-
dc.subject.keywordAuthorHomo-dimer-
dc.subject.keywordAuthorBlood circulation time-
dc.subject.keywordAuthorSpytag-spycatcher-
dc.subject.keywordAuthorTherapeutic efficacy-
dc.subject.keywordPlusFC-FUSION PROTEINS-
dc.subject.keywordPlusBINDING-PROTEINS-
dc.subject.keywordPlusHALF-LIFE-
dc.subject.keywordPlusTHERAPEUTIC PROTEINS-
dc.subject.keywordPlusALBUMIN-BINDING-
dc.subject.keywordPlusSCAFFOLDS-
dc.subject.keywordPlusANTIBODIES-
dc.subject.keywordPlusAFFINITY-
dc.subject.keywordPlusPEGYLATION-
dc.subject.keywordPlusSTRATEGY-
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