A Novel Dendritic Cell Population Generated by Fusing Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-21 Induces Tumor-Antigen Specific Immunity

Cancer recruits the immune system to promote its growth and to inhibit reactions against itself. We generated a fusion of GMCSF and IL-21 (GIFT-21) with the aim of stimulating distinct, but complementary, elements of the innate and adaptive immune system against cancer. In a previous study, GIFT-21's aberrant interactions with its cognate receptors on macrophages resulted in an unanticipated pro-inflammatory response and tumor rejection in mice.

We further explored this phenomenon by treating mice with dendritic cells (DC) derived by treating monocytes with GIFT-21. B16 melanoma and D2F2/neu breast cancer growth was inhibited only in mice treated with a single injection of antigen naïve GIFT-21 DCs. This effect was lost in CD8-/- and CCR2-/- mice and when mice were treated with β2 microglobulin deficient GIFT-21 DCs, and we confirmed that GIFT-21 DCs migrated to and sampled from the tumors to present tumor antigens to CCL2 recruited CD8+ T cells via MHCI.

When stimulated with GIFT-21 DCs, the immune system can identify cancer specifically, independently of cancer type. We conclude that GIFT-21 and its associated cellular products may serve as novel therapeutic platforms for the treatment of cancer.

No relevant conflicts of interest to declare.