The induction of a cellular Mage-specific immunresponce by lentiviral transduction of dendritic cells.

Dendritic cells (DC) are pivotal regulators of immune reactivity. The observation that DC can recruit naive T cells has invigorated cancer immunology and led to the proposal of DC as the basis for anti-cancer vaccines. Designing effective strategies to load DC with antigens is a challenging field of research. Therefore, we optimised the lentiviral vector system and showed that efficient gene transfer in DC can be obtained without adverse effects. We further showed that DC transduced with triple helix containing, self-inactivating lentiviruses encoding the fusionprotein Ii80MAGE-A3 were potent inducers of MAGE-A3 specific CD4+ and CD8+ T cells. Moreover, we isolated a MAGE-A3 specific cytotoxic T lymphocyte (CTL) clone that recognised peptide EGDCAPEEK, which is encoded by several MAGE-genes, presented by HLA-Cw7 molecules, efficiently processed in tumor cells and therefore can be used as a target for anti-tumoral vaccination.
In a second part of the thesis we compared side-by-side DC generated in the presence of IL-4/GM-CSF to DC generated in the presence of IL-3/IFNb and showed that the latter were more potent inducers of Mel-A specific CTL.
In conclusion, combining the unique characteristics of DC with the advantages of the lentiviral vector system could lead to a potent anti-tumor vaccine.