Journal
MOLECULAR THERAPY-ONCOLYTICS
Volume 18, Issue -, Pages 326-334Publisher
CELL PRESS
DOI: 10.1016/j.omto.2020.07.002
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Funding
- Stop Cancer
- Rosalinde and Arthur Gilbert Foundation
- California Institute of Regenerative Medicine
- Alvarez Family Foundation
- Anthony F. & Susan M. Markel Foundation
- Ben and Catherine Ivy Foundation, City of Hope
- National Cancer Institute [R43CA86768, R44CA8678, R01CA197359]
- National Cancer Institute of the NIH [P30CA033572]
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Oncolytic virotherapy represents 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, which reduces viral delivery to the tumor. Patient-derived mesenchymal stem cells that home to tumors have been used as viral delivery tools, but variability associated with autologous cell isolations limits the clinical applicability of this approach. We previously developed an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) that can be used to deliver viral cargo. Here, we demonstrate that this NSC line can improve the delivery of a thymidine kinase gene-deficient conditionally replication-competent orthopoxvirus, CF33, in a preclinical cisplatin-resistant peritoneal ovarian metastases model. Overall, our findings provide the basis for using off-the-shelf allogeneic cell-based delivery platforms for oncolytic viruses, thus providing a more efficient delivery alternative compared with the free virus administration approach.
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