Cowpea Mosaic Virus Promotes Anti-Tumor Activity and Immune Memory in a Mouse Ovarian Tumor Model

Cowpea mosaic virus (CPMV) is a promising platform nanotechnology with applications as a cancer therapeutic. To understand the therapeutic potential of CPMV in more detail, its antitumor mechanisms are investigated using a syngeneic immunocompetent murine orthotopic ovarian cancer model (ID8-Defb29/Vegf-A). CPMV treatment in situ promotes tumor regression and prevents tumor recurrence. Although CPMV does not kill tumor cells directly, it promotes an intra-tumoral cytokine response which induces pre-existing myeloid cells to break immunotolerance and initiate antitumor responses. The upregulation of interleukin-6 and interferon-γ as well as the downregulation of IL-10 and transforming growth factor β are observed, associated with activation and repolarization of tumor-associated macrophages and neutrophils to an anti-tumor phenotype. Furthermore, the in situ administration of CPMV recruits dendritic cells and natural killer cells to the tumor site, and induces the expression of costimulatory molecules on CD11b^- myeloid cells. By converting immunosuppressive myeloid cells into potent antigen-presenting cells, in situ CPMV treatment significantly improves effector and memory CD4⁺ and CD8⁺ T cell responses and promoted systemic tumor-specific cytotoxic CD8⁺ T cell activity. CPMV in situ immunotherapy induces significant tumor control in an aggressive ovarian tumor model by coordinating innate and adaptive immune responses involving neutrophils, macrophages, and T cells.