The aim of this project was to optimize the anti-tumor immune response induced by dendritic and iNKTs cells, in response to KRN7000 (a-galactosyl-ceramide), which interacts with CD1d molecule situated on DCs. At first we synthesized new analogues of KRN7000, by functionalizing the C6 position of the carbohydrate moiety and by grafting a phenyl group on one of the fatty chain. In vitro studies indicated that chemical modifications of KRN7000 did not alter its interaction with CD1d. In all cases, cytokine secretion was observed. Further studies are in progress to describe the in vivo cytokine profile. In a second step, we developed liposomal constructs incorporating KRN7000 to optimize its presentation to DCs. Some constructions containing KRN7000 were able to associate a peptide, a targetting molecule of DCs or TLR ligands. Even if the anergy phenomenon induced by repeated administrations of KRN7000 could not be regulated by the use of liposomes, we have shown that encapsulated KRN7000 is still supported by DCs and that an immune response resulting in cytokines secretion by iNKT cells is induced.
