Drug Conjugates for Targeting Eph Receptors in Glioblastoma
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 syst...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/4/77 |
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| author | Puja Sharma Callie Roberts Denise Herpai Izabela D. Fokt Waldemar Priebe Waldemar Debinski |
| author_facet | Puja Sharma Callie Roberts Denise Herpai Izabela D. Fokt Waldemar Priebe Waldemar Debinski |
| author_sort | Puja Sharma |
| collection | DOAJ |
| description | 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 IC<sub>50</sub> 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. |
| first_indexed | 2024-03-10T20:17:03Z |
| format | Article |
| id | doaj.art-11a5f4d263a04036a3c5e2005bb13c29 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:17:03Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-11a5f4d263a04036a3c5e2005bb13c292023-11-19T22:27:58ZengMDPI AGPharmaceuticals1424-82472020-04-011347710.3390/ph13040077Drug Conjugates for Targeting Eph Receptors in GlioblastomaPuja Sharma0Callie Roberts1Denise Herpai2Izabela D. Fokt3Waldemar Priebe4Waldemar Debinski5Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USABrain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USABrain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USADepartment of Experimental Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Experimental Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX 77054, USABrain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC 27157, USAGlioblastoma (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 IC<sub>50</sub> 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.https://www.mdpi.com/1424-8247/13/4/77Eph receptorsmultiple-receptor targetingglioblastomaligand–drug conjugatesdoxorubicin |
| spellingShingle | Puja Sharma Callie Roberts Denise Herpai Izabela D. Fokt Waldemar Priebe Waldemar Debinski Drug Conjugates for Targeting Eph Receptors in Glioblastoma Pharmaceuticals Eph receptors multiple-receptor targeting glioblastoma ligand–drug conjugates doxorubicin |
| title | Drug Conjugates for Targeting Eph Receptors in Glioblastoma |
| title_full | Drug Conjugates for Targeting Eph Receptors in Glioblastoma |
| title_fullStr | Drug Conjugates for Targeting Eph Receptors in Glioblastoma |
| title_full_unstemmed | Drug Conjugates for Targeting Eph Receptors in Glioblastoma |
| title_short | Drug Conjugates for Targeting Eph Receptors in Glioblastoma |
| title_sort | drug conjugates for targeting eph receptors in glioblastoma |
| topic | Eph receptors multiple-receptor targeting glioblastoma ligand–drug conjugates doxorubicin |
| url | https://www.mdpi.com/1424-8247/13/4/77 |
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