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Drug Conjugates for Targeting Eph Receptors in Glioblastoma.

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.

SUBMITTER: Sharma P

PROVIDER: S-EPMC7243104 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Drug Conjugates for Targeting Eph Receptors in Glioblastoma.

Sharma Puja P Roberts Callie C Herpai Denise D Fokt Izabela D ID Priebe Waldemar W Debinski Waldemar W

Pharmaceuticals (Basel, Switzerland) 20200423 4

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 ...[more]

PMID: 32340173

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