Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates

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dc.contributor.authorJongjin Park-
dc.contributor.authorNa Geum Lee-
dc.contributor.authorMihee Oh-
dc.contributor.authorJinhoi Song-
dc.contributor.authorWooil Kim-
dc.contributor.authorMin-Gi Kwon-
dc.contributor.authorSeul Gi Kim-
dc.contributor.authorBaek Soo Han-
dc.contributor.authorKwang-Hee Bae-
dc.contributor.authorDong Gwang Lee-
dc.contributor.authorSang Hyun Lee-
dc.contributor.authorJong Gil Park-
dc.contributor.authorJ H Kim-
dc.contributor.authorJangwook Lee-
dc.contributor.authorJeong Ki Min-
dc.date.accessioned2020-09-24T04:03:20Z-
dc.date.available2020-09-24T04:03:20Z-
dc.date.issued2020-
dc.identifier.issn0142-9612-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/22792-
dc.description.abstractThe self-renewal properties of human pluripotent stem cells (hPSCs) contribute to their efficacy in tissue regeneration applications yet increase the likelihood of teratoma formation, thereby limiting their clinical utility. To address this issue, we developed a tool to specifically target and neutralize undifferentiated hPSCs, thereby minimizing tumorigenicity risk without negatively affecting regenerated and somatic tissues. Specifically, we conjugated a monoclonal antibody (K6-1) previously generated in our laboratory against desmoglein 2 (Dsg2), which is highly differentially expressed in undifferentiated hPSCs versus somatic tissues, to the chemotherapeutic agent doxorubicin (DOX). The K6-1-DOX conjugates were selectively targeted and incorporated into Dsg2-positive hPSCs, leading to pH-dependent endosomal release and nuclear localization of DOX with subsequent cytotoxicity via an apoptotic caspase cascade. Conversely, Dsg2-negative fibroblasts showed minimal conjugate uptake or cytotoxicity, suggesting that K6-1-DOX treatment would yield few side effects owing to off-target effects. Selective removal of undifferentiated stem cells was also supported by in vivo studies using a mouse xenograft model, wherein hIgG-DOX- but not K6-1-DOX-pretreated-hPSC injection led to teratoma development. Together, these results validated the ability of the Dsg2-targeted antibody-anticancer drug conjugate to facilitate the safety of stem cell therapies.-
dc.publisherElsevier-
dc.titleSelective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates-
dc.title.alternativeSelective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates-
dc.typeArticle-
dc.citation.titleBiomaterials-
dc.citation.number0-
dc.citation.endPage120265-
dc.citation.startPage120265-
dc.citation.volume259-
dc.contributor.affiliatedAuthorJongjin Park-
dc.contributor.affiliatedAuthorNa Geum Lee-
dc.contributor.affiliatedAuthorMihee Oh-
dc.contributor.affiliatedAuthorJinhoi Song-
dc.contributor.affiliatedAuthorWooil Kim-
dc.contributor.affiliatedAuthorMin-Gi Kwon-
dc.contributor.affiliatedAuthorSeul Gi Kim-
dc.contributor.affiliatedAuthorBaek Soo Han-
dc.contributor.affiliatedAuthorKwang-Hee Bae-
dc.contributor.affiliatedAuthorDong Gwang Lee-
dc.contributor.affiliatedAuthorSang Hyun Lee-
dc.contributor.affiliatedAuthorJong Gil Park-
dc.contributor.affiliatedAuthorJangwook Lee-
dc.contributor.affiliatedAuthorJeong Ki Min-
dc.contributor.alternativeName박종진-
dc.contributor.alternativeName이나금-
dc.contributor.alternativeName오미희-
dc.contributor.alternativeName송진회-
dc.contributor.alternativeName김우일-
dc.contributor.alternativeName권민기-
dc.contributor.alternativeName김슬기-
dc.contributor.alternativeName한백수-
dc.contributor.alternativeName배광희-
dc.contributor.alternativeName이동광-
dc.contributor.alternativeName이상현-
dc.contributor.alternativeName박종길-
dc.contributor.alternativeName김재호-
dc.contributor.alternativeName이장욱-
dc.contributor.alternativeName민정기-
dc.identifier.bibliographicCitationBiomaterials, vol. 259, pp. 120265-120265-
dc.identifier.doi10.1016/j.biomaterials.2020.120265-
dc.subject.keywordAntibody-drug conjugates-
dc.subject.keywordTargeted delivery-
dc.subject.keywordPluripotent stem cell-
dc.subject.keywordDesmoglein-2-
dc.subject.keywordTeratoma elimination-
dc.subject.localAntibody-drug conjugates-
dc.subject.localantibody-drug conjugate-
dc.subject.localAntibody-drug conjugate-
dc.subject.localTargeted delivery-
dc.subject.localPluripotent stem cell-
dc.subject.localPluripotent stem cells-
dc.subject.localpluripotent stem cells-
dc.subject.localpluripotent stem cell-
dc.subject.localPluripotent Stem Cell-
dc.subject.localdesmoglein-2-
dc.subject.localDesmoglein-2-
dc.subject.localTeratoma elimination-
dc.subject.localTeratoma elimination-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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