IMMUNOBIOLOGY In vivo manipulation of dendritic cells to induce therapeutic immunity

Efficient antigen presentation and T-cell priming are essential components of ef-fective antitumor immunity. Dendritic cells are critical to both of these functions but to date no method has been devised that both targets antigen to these cells and activates them, in situ, in a manner that induces systemic immunity. In this study we combined a dendritic cell growth fac-tor, Flt3 ligand, with a dendritic cell activa-tor, immunostimulatory DNA, and a tumor antigen to activate and load dendritic cells in vivo. Initial studies showed that immunostimulatory DNA not only acti-vates dendritic cells but also prolongs their survival in vivo and in vitro. Follow-ing treatment of mice with Flt3 ligand, coadministration of immunostimulatory DNA and antigen induced potent antitu-mor immunity, resulting in both tumor prevention and regression of existing tu-mors. CD8 cytotoxic T lymphocytes but not CD4 T cells were required for tumor protection. Natural killer cells also contrib-uted to tumor protection. These results show that dendritic cells can be loaded with antigen and activated, in situ, and provide the basis for dendritic cell- tar-geted clinical strategies. (Blood. 2002;99