Marine-derived sulfoglycolipids with immunomodulant activities and their development as vaccines in immunotherapy

Glycolipids are primary metabolites present in all living organisms and characterized by interesting biological properties.1,2 In recent years, glycoglycerolipids and ceramides have attracted particular interest as either agonists of cellular receptors, e.g. Toll-Like Receptors (TLRs) and MHC-related glycoproteins of the CD1 family, or chemical entities for the development of anti-tumoral and immunological drugs.3 In the last years, we have focused our study on the immunological properties of 6'-sulfoquinovosyldiacylglycerols analogs, plant glycoglycerolipids that have wide distribution in terrestrial and marine photosynthetic organisms. This communication summarizes our work about the synthetic challenges associated with the preparation and development of this family of molecules and their use as molecular adjuvants of vaccines4. In particular we report synthesis and activity of a chimeric immunomodulatory sulfolipid named ?-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. ?-SQDG18 induces maturation of DC with expression of high levels of MHC II molecules and upregulation of costimulatory proteins (CD83, CD86) and proinflammatory cytokines (IL-12 and INF-?). Mice immunized with OVA associated to ?-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice by ?-SQDG18-adjuvanted hgp10 peptide elicited a protective response with reduction of tumour growth and increase of survival.