Manipulation of the Tumor Immunomicroenvironment Using Nanovaccination

Abstract

Cancer immunotherapy is an attractive approach for treating cancer where the host immune system is activated to combat the cancer. Here, we report on the development of a liposome-based nanovaccines formulation consisting of DOTAP (1, 2-dioleoyl-3-trimethylammonium-propane) which has some immunogenicity as well as certain levels of cell death ability, and an adjuvant, MPL-A (monophosphoryl lipid A), a toll like receptor-4 agonist and IL-12, an immunomodulatory agent. The result shows that localized treatment of mice bearing oorthotopic 4T1 breast tumors with the nanovaccines elicit an antigen-specific cytotoxic T-cell response, abrogating the tumor significantly as compared with single agent treatment. Immunohistochemistry data shows the treatment inhibits proliferation of tumor cells and causes infiltration of cancer-fighting immune cells such as cytotoxic (Tc) cells. In summary, an MPL-IL-12-liposome cancer nanovaccine drastically decreases tumor size and manipulates the tumor immunomicroenvironment by decreasing cancer cell proliferation and increasing stimulation of cancer fighting immune cells, as well as increasing expression of iNOS.