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Poster Display session 1

5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Pathology/Molecular Biology

Tumour Site

Presenters

Alessandra Affinito

Citation

Annals of Oncology (2019) 30 (suppl_5): v797-v815. 10.1093/annonc/mdz269

Authors

A. Affinito1, C. Quintavalle1, C.L. Esposito2, G. Roscigno3, C. Vilardo3, S. Nuzzo4, L. Ricci Vitiani5, G. De Luca5, Z. Minic6, S. Giannetti7, R. Pallini8, M.V. Berezovski6, A.S. Kichkailo9, I.N. Lapin10, V. De Franciscis2, G. Condorelli11

Author affiliations

  • 1 ., Percuros BV, 2333BZ - LEIDEN/NL
  • 2 ., IEOS CNR, 80131 - Naples/IT
  • 3 Dipartimento Di Medicina Molecolare E Biotecnologie Mediche, Università degli Studi di Napoli Federico II - Scuola di Medicina e Chirurgia, 80131 - Napoli/IT
  • 4 ., IRCCS SDN SpA, 80143 - Naples/IT
  • 5 Department Of Hematology, Oncology And Molecular Medicine, Istituto Superiore di Sanità, 00161 - Rome/IT
  • 6 Department Of Chemistry And Biomolecular Sciences And John L. Holmes Mass Spectrometry Facility, University of Ottawa, K1N6N5 - Ottawa/CA
  • 7 Institute Of Anatomy And Cell Biology, Universitá Cattolica del Sacro Cuore, 00161 - Rome/IT
  • 8 Institute Of Neurosurgery, Università Cattolica del Sacro Cuore, 00161 - Rome/IT
  • 9 2krasnoyarsk State Medical University Named After Prof. V.f. Voino-yaseneck, Academy of Science, 660010 - Krasnoyarsk/RU
  • 10 Siberian Physical-technical Institute, Tomsk State University, 634003 - Tomsk/RU
  • 11 Department F Molecular Medicine And Medical Biotechnology, Università degli Studi di Napoli Federico II, 80131 - Naples/IT

Resources

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Abstract 5743

Background

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal. It has been demonstrated that the modest benefit of conventional therapies is due to the presence of glioblastoma stem cells (GSCs) that cause tumor relapse and chemoresistance. Thus, the identification of specific ligands for GSCs could be fundamental for GBM improvement in survival.

Methods

Here, using a cell-SELEX approach on human primary GSCs, we generated RNA aptamers –namely, a 40L sequence and A40s, a truncated form– that bind GSCs.

Results

The aptamers were selective for human GSCs, they were able to inhibit stemness, cell growth and migration, and strongly reduced tumor proliferation in vivo. Moreover, 40L and A40s were rapidly internalized upon target binding and, therefore, may serve as selective vehicles for therapeutics. Furthermore, A40s is able to cross the blood brain barrier (BBB). Using several approaches, we have identified the aptamer target in the Ephrin type-A receptor 2 (EphA2) which is overexpressed in GSCs compared to differentiated cells.

Conclusions

Given the role of GSCs in GBM recurrence and therapy resistance, 40L and A40s represent innovative therapeutic and diagnostic tool for GBM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Gerolama Condorelli.

Funding

Federico II, Naples.

Disclosure

All authors have declared no conflicts of interest.

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