Although anti-tumor activity of HSV-1 ICP0 null oncolytic vectors has been validated in murine breast cancer models, oncolytic virus treatment alone is insufficient to break immune tolerance. Thus, we investigated enhancing efficacy through combination therapy with the immunogenic cell death inducing chemotherapeutic drug, mitoxantrone. Despite a lack of enhanced cytotoxicity in vitro, HSV-1 ICP0 null oncolytic virus KM100 with 5 μM mitoxantrone provided significant survival benefit to BALB/c mice bearing Her2/neu TUBO-derived tumors. This protection was mediated by increased intra-tumoral infiltration of neutrophils and tumor antigen specific CD8+ T cells. Depletion studies verified that CD8, CD4, and Ly6G expressing cells are essential for enhanced efficacy of combination therapy. Moreover, the addition of mitoxantrone to KM100 oncolytic virus treatment broke immune tolerance in BALB-neuT mice bearing TUBO-derived tumors. This study suggests that oncolytic viruses in combination with immunogenic cell death inducing chemotherapeutics enhance the immunogenicity of the tumor-associated antigens, breaking immunological tolerance established towards these antigens.
- Received May 17, 2013.
- Revision received August 1, 2013.
- Accepted August 12, 2013.
- Copyright © 2013, American Association for Cancer Research.