Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration

Dendritic cells (DCs) are professional antigen-presenting cells, well equip ped to initiate an immune response. Currently, tumor antigen-derived peptid e loaded DCs are used in clinical vaccination in cancer patients. However, the optimal dose and route of administration of a DC vaccine still remain t o be determined. Using indium-111-labeled DCs, we investigated whether the route of administration does affect the biodistribution of DCs in lymphoid organs and whether it influences the outcome of DC vaccination in the B16 m ouse melanoma tumor model. The results demonstrate that i.v. injected DCs m ainly accumulate in the spleen, whereas s.c. injected DCs preferentially ho me to the T-cell areas of the draining lymph nodes. Using tyrosinase-relate d protein-2-derived peptide-loaded DC vaccination in a fully autologous B16 melanoma tumor model, we observed a delay in tumor growth, improved surviv al as well as increased antitumor cytotoxic T-cell reactivity after s.c. va ccination as compared to i.v. vaccination. These data demonstrate that opti mal induction of antitumor reactivity against the autologous melanocyte dif ferentiation antigen tyrosinase-related protein-2-derived peptitde occurs a fter s.c. vaccination and correlates with the preferential accumulation of DCs in the T-cell areas of lymph nodes.