Synergistic Activation of Antitumor Immunity by a Particulate Therapeutic Vaccine

Abstract

Success in anticancer immune therapy relies on stimulation of tumor antigen-specific T lymphocytes and effective infiltration of the T cells into tumor tissue. Here, a therapeutic vaccine that promotes proliferation and tumor infiltration of antigen-specific T cells in both inflamed and noninflamed tumor types is described. The vaccine consists of STING agonist 2'3'-cGAMP, TLR9 ligand CpG, and tumor antigen peptides that are loaded into nanoporous microparticles (<i>μ</i>GCVax). <i>μ</i>GCVax is effective in inhibiting lung metastatic melanoma, primary breast cancer, and subcutaneous colorectal cancer in their respective murine models, including functional cure of HER2-positive breast cancer. Mechanistically, <i>μ</i>GCVax potently stimulates type I interferon expression in dendritic cells, and promotes CD8⁺ and CD103⁺ dendritic cell maturation and migration to lymph nodes and other lymphatic tissues. Antitumor responses are dependent on TLR9 and interferon <i>α</i>/<i>β</i> receptor signaling, and to a less extent on STING signaling. These results demonstrate a high potential for <i>μ</i>GCVax in mediating antitumor immunity in personalized cancer therapy.