Oncolytics Biotech Inc. (ONCY)

[onco_investor]

Ovarian Cancer Reovirus Research in Molecular Therapy

Pre-Clinical research of the Reovirus in Dr. Patrick Lee's lab along with Dr. Gujar

http://www.nature.com/mt/journal/v21/n2/abs/mt2012228a.html

Original Article

Subject Category: Vector Toxicology, Immunogenicity and Safety

Molecular Therapy (2013); 21 2, 338–347. doi:10.1038/mt.2012.228

Multifaceted Therapeutic Targeting of Ovarian Peritoneal Carcinomatosis Through Virus-induced Immunomodulation

Shashi Gujar1, Rebecca Dielschneider1,2, Derek Clements3, Erin Helson1, Maya Shmulevitz4, Paola Marcato3, Da Pan1, Lu-zhe Pan1, Dae-Gyun Ahn1, Abdulaziz Alawadhi1 and Patrick WK Lee1,3

1Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
2Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
3Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
4Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
Correspondence: Patrick WK Lee, Professor and Cameron Chair in Basic Cancer Research, Dalhousie University, Department of Microbiology and Immunology, 7P, Charles Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 1X5, Canada. E-mail: [e-mail]

Received 4 August 2012; Accepted 7 October 2012
Advance online publication 13 November 2012

Abstract
Immunosuppression associated with ovarian cancer (OC) and resultant peritoneal carcinomatosis (PC) hampers the efficacy of many promising treatment options, including immunotherapies. It is hypothesized that oncolytic virus-based therapies can simultaneously kill OC and mitigate immunosuppression. Currently, reovirus-based anticancer therapy is undergoing phase I/II clinical trials for the treatment of OC. Hence, this study was focused on characterizing the effects of reovirus therapy on OC and associated immune microenvironment. Our data shows that reovirus efficiently killed OC cells and induced higher expression of the molecules involved in antigen presentation including major histocompatibility complex (MHC) class I, ß2-microglobulin (ß2M), TAP-1, and TAP-2. In addition, in the presence of reovirus, dendritic cells (DCs) overcame the OC-mediated phenotypic suppression and successfully stimulated tumor-specific CD8+ T cells. In animal studies, reovirus targeted local and distal OC, alleviated the severity of PC and significantly prolonged survival. These therapeutic effects were accompanied by decreased frequency of suppressive cells, e.g., Gr1.1+, CD11b+ myeloid derived suppressor cells (MDSCs), and CD4+, CD25+, FOXP3+ Tregs, tumor-infiltration of CD3+ cells and higher expression of Th1 cytokines. Finally, reovirus therapy during early stages of OC also resulted in the postponement of PC development. This report elucidates timely information on a therapeutic approach that can target OC through clinically desired multifaceted mechanisms to better the outcomes.