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Tumor-associated antigens offer an opportunity to selectively target various components of the GBM microenvironment while sparing the normal cells within the central nervous system. In this study, we conjugated a multivalent vector protein, QUAD 3.0, that can target four receptors: EphA3, EphA2, EphB2, and also IL-13RA2, spanning virtually 100% of the GBM microenvironment, to doxorubicin derivatives. The conjugates effectively bound to all four receptors, although to varying degrees, and delivered cytotoxic loads to both established and patient-derived GBM cell lines, with IC50 values in the low nM range. The conjugates were also non-toxic to animals. We anticipate that the QUAD 3.0 Dox conjugates will be further used in preclinical models and possibly clinics in the foreseeable future.<\/jats:p>","DOI":"10.3390\/ph13040077","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"77","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Drug Conjugates for Targeting Eph Receptors in Glioblastoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Puja","family":"Sharma","sequence":"first","affiliation":[{"name":"Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-8526","authenticated-orcid":false,"given":"Callie","family":"Roberts","sequence":"additional","affiliation":[{"name":"Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Herpai","sequence":"additional","affiliation":[{"name":"Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela D.","family":"Fokt","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Priebe","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Debinski","sequence":"additional","affiliation":[{"name":"Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.5483\/BMBRep.2011.44.3.158","article-title":"Glioblastoma multiforme: A perspective on recent findings in human cancer and mouse models","volume":"44","author":"Lim","year":"2011","journal-title":"BMB Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1093\/neuonc\/nov297","article-title":"American brain tumor association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008\u20132012","volume":"18","author":"Ostrom","year":"2016","journal-title":"Neuro. 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