Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Shiran Ferber, Galia Tiram, Ana Sousa-Herves, Anat Eldar-Boock, Adva Krivitsky, Anna Scomparin, Eilam Yeini, Paula Ofek, Dikla Ben-Shushan, Laura Isabel Vossen, Kai Licha, Rachel Grossman, Zvi Ram, Jack Henkin, Eytan Ruppin, Noam Auslander, Rainer Haag, Marcelo Calderón, Ronit Satchi-Fainaro*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Glioblastoma is a highly aggressive brain tumor. Current standard-of-care results in a marginal therapeutic outcome, partly due to acquirement of resistance and insufficient blood-brain barrier (BBB) penetration of chemotherapeutics. To circumvent these limitations, we conjugated the chemotherapy paclitaxel (PTX) to a dendritic polyglycerol sulfate (dPGS) nanocarrier. dPGS is able to cross the BBB, bind to P/L-selectins and accumulate selectively in intracranial tumors. We show that dPGS has dual targeting properties, as we found that P-selectin is not only expressed on tumor endothelium but also on glioblastoma cells. We delivered dPGS-PTX in combination with a peptidomimetic of the anti-angiogenic protein thrombospondin-1 (TSP-1 PM). This combination resulted in a remarkable synergistic anticancer effect on intracranial human and murine glioblastoma via induction of Fas and Fas-L, with no side effects compared to free PTX or temozolomide. This study shows that our unique therapeutic approach offers a viable alternative for the treatment of glioblastoma.

Original languageEnglish (US)
Article numbere25281
JournaleLife
Volume6
DOIs
StatePublished - Oct 4 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Ferber, S., Tiram, G., Sousa-Herves, A., Eldar-Boock, A., Krivitsky, A., Scomparin, A., Yeini, E., Ofek, P., Ben-Shushan, D., Vossen, L. I., Licha, K., Grossman, R., Ram, Z., Henkin, J., Ruppin, E., Auslander, N., Haag, R., Calderón, M., & Satchi-Fainaro, R. (2017). Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome. eLife, 6, [e25281]. https://doi.org/10.7554/eLife.25281