Combining Oncolytic HSV-1 with Immunogenic Cell Death-Inducing Drug Mitoxantrone Breaks Cancer Immune Tolerance and Improves Therapeutic Efficacy

摘要: Although antitumor activity of herpes simplex virus 1 (HSV-1) ICP0 null oncolytic vectors has been validated in murine breast cancer models, 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 enhanced cytotoxicity vitro, HSV-1 KM100 5 μmol/L mitoxantrone provided significant survival benefit BALB/c mice bearing Her2/neu TUBO-derived tumors. This protection was mediated by increased intratumoral infiltration neutrophils and tumor antigen-specific CD8(+) T cells. Depletion studies verified that CD8-, CD4-, Ly6G-expressing cells are essential for therapy. Moreover, addition broke tolerance BALB-neuT study suggests viruses chemotherapeutics enhance immunogenicity tumor-associated antigens, breaking immunologic established toward these antigens.