Oncolytics Biotech Inc. (ONCY)

[onco_investor]

Reovirus delivery using Dendritic Cells (DC)

Internalization of Oncolytic Reovirus by Human Dendritic Cell Carriers Protects the Virus from Neutralization

http://clincancerres.aacrjournals.org/content/early/2011/03/09/1078-0432.CCR-10-3266.abstract

Elizabeth J. Ilett1, Montserrat Barcena2, Fiona Errington-Mais1, Stephen Griffin1, Kevin J. Harrington3, Hardev S. Pandha4, Matthew Coffey5, Peter J. Selby6, Ronald W.A.L. Limpens2, Mieke Mommaas2, Rob C. Hoeben7, Richard G. Vile8, and Alan A. Melcher9,*
+ Author Affiliations

1Leeds Institute of Molecular Medicine, University of Leeds
2Dept of Molecular Cell Biology, Leiden University Medical Centre
3Targeted Therapy Team, The Institute of Cancer Research
4Oncology, Post Graduate Medical School, University of Surrey
5Oncology, Oncolytics Biotech Inc
6CRUK Clinical Centre, University of Leeds
7Molecular Cell Biology, Leiden University Medical Centre
8Molecular Medicine, Mayo Clinic
9Oncology Unit, St James's University Hospital
* Corresponding Author:
Alan A. Melcher, Oncology Unit, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, United Kingdom [e-mail]
Abstract

Purpose: Dendritic cells may be the most effective way of delivering oncolytic viruses to patients. Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing anti-viral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility using a variety of cell types and viruses. This study addressed the efficacy of human dendritic cells (DC) to transport virus in the presence of human neutralizing serum.

Experimental Design: Following reovirus-loading, DC or T cells were co-cultured with melanoma cells ± neutralizing serum; the melanoma cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated using labelled tumour cells and the ability of reovirus-loaded DC to prime T cells was also investigated. Results: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for melanoma cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific anti-tumour immune responses.

Conclusions: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for metastatic disease with induction of an anti-tumour immune response.

Received December 10, 2010.
Revision received February 18, 2011.
Accepted February 25, 2011.

American Association for Cancer Research.