Enhanced Delivery of Oncolytic Adenovirus by Neural Stem Cells for Treatment of Metastatic Ovarian Cancer

Rachael Mooney*, Asma Abdul Majid, Jennifer Batalla-Covello, Diana Machado, Xueli Liu, Joanna Gonzaga, Revathiswari Tirughana, Mohamed Hammad, Thanh H. Dellinger, Maciej S. Lesniak, David T. Curiel, Karen S. Aboody

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Oncolytic virotherapy is a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance or neutralization of the virus, which reduces viral access to tumor foci. To overcome this barrier, patient-derived mesenchymal stem cells have been used to deliver virus to tumors, but variability associated with autologous cell isolations prevents this approach from being broadly clinically applicable. Here, we demonstrate the ability of an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) to protect oncolytic viral cargo from neutralizing antibodies within patient ascites fluid and to deliver it to tumors within preclinical peritoneal ovarian metastases models. The viral payload used is a conditionally replication-competent adenovirus driven by the survivin promoter (CRAd-S-pk7). Because the protein survivin is highly expressed in ovarian cancer, but not in normal differentiated cells, viral replication should occur selectively in ovarian tumor cells. We found this viral agent was effective against cisplatin-resistant ovarian tumors and could be used as an adjunct treatment with cisplatin to decrease tumor burden without increasing toxicity. Collectively, our data suggest NSC-delivered CRAd-S-pk7 virotherapy holds promise for improving clinical outcome, reducing toxicities, and improving quality of life for patients with advanced ovarian cancer.

Original languageEnglish (US)
Pages (from-to)79-92
Number of pages14
JournalMolecular Therapy - Oncolytics
Volume12
DOIs
StatePublished - Mar 29 2019

Keywords

  • CRAd-S-pk7
  • cellular therapy
  • neural stem cells
  • oncolytic virotherapy
  • ovarian cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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