期刊
ADVANCED THERAPEUTICS
卷 2, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/adtp.201900003
关键词
cancer immunotherapy; in situ vaccination; ovarian cancer; plant virus; tumor infiltrating neutrophils
资金
- National Institutes of Health [U01-CA218292]
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-gamma as well as the downregulation of IL-10 and transforming growth factor beta 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.
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