Figure 1: Conventional and in situ vaccination can be used to induce anti-cancer T cell immunity.

Conventional vaccines often use tumor antigens identified from biopsies, which are manufactured in one of several common formats (e.g., peptide/protein, nucleic acid, viral vector or dendritic cell-based) and then administered in the skin or muscle to prime anti-cancer T cells in lymph nodes. In contrast, in situ vaccination involves (1) delivery of immunostimulants or cytotoxic chemotherapeutics into tumors to (2) kill cancer cells, as well as deplete suppressor cells (MDSCs, Tregs) and/or promote immunogenic cancer cell death. Immunogenic cancer cell death is characterized by both the translocation of calreticulin (CRT) to cancer cell surfaces, which promotes their uptake by dendritic cells (DCs), as well as cancer cell release of danger associated molecular patterns (DAMPs) that recruit and activate immune cells. Activated DCs loaded with tumor antigens migrate to draining lymph nodes and prime anti-cancer T cells (3) that hone to tumors and kill cancer cells. The accompanying table summarizes different types of conventional and in situ vaccines that have been used for inducing T cell immunity.