Abstract
Abstract 5177
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.
Author notes
Asterisk with author names denotes non-ASH members.
