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 (GCVax).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,GCVax potently stimulates type I interferon expression in dendritic cells, and promotes CD8and CD103dendritic cell maturation and migration to lymph nodes and other lymphatic tissues. Antitumor responses are dependent on TLR9 and interferon/receptor signaling, and to a less extent on STING signaling. These results demonstrate a high potential forGCVax in mediating antitumor immunity in personalized cancer therapy.