Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells

Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8(+) T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 x 10(6) s.c. followed by two i.v. ones of 6 and 12 x 10(6), respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2.1-positive control peptides as well as the recall Ag tetanus toroid (in three of eight patients) generated in all eight patients Ag-specific effector CD8(+) T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-gamma -producing, effector CD8(+) T cells have been reliably observed in patients vaccinated with melanoma Ags, Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.