Drug conjugates for targeting EPH receptors in glioblastoma

Puja Sharma, Callie Roberts, Denise Herpai, Izabela D. Fokt, Waldemar Priebe, Waldemar Debinski

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Glioblastoma (GBM) is a complex and heterogeneous tumor that warrants a comprehensive therapeutic approach for treatment. 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.

Original languageEnglish (US)
Article number77
JournalPharmaceuticals
Volume13
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Doxorubicin
  • Drug conjugates
  • Eph receptors
  • Glioblastoma
  • Ligand
  • Multiple-receptor targeting

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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