Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells.

Juliette Angel (1, 2) , Laurence Chaperot (1, 2) , Jean-Paul Molens (1, 2) , Paulette Mezin (3) , Mario Amacker (4) , Rinaldo Zurbriggen (4) , Alexei Grichine (1) , Joël Plumas (1)

1 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
2 Laboratoire recherche et développement
3 Département d'anatomie et cythologie pathologique
4 Pevion Biotech Ltd

Cytotoxic T lymphocytes (CTL) are crucial in viral clearance and tumor growth control. Thus the induction of CTL activity is an important aim in vaccine development. We investigate an innovative delivery system for peptide transfer to the MHC class I processing pathway of APC with the aim to trigger CTL in the context of an antitumoral response. The strategy relies on a novel antigen delivery system termed "chimeric immunopotentiating reconstituted influenza virosomes" (CIRIV) targeting plasmacytoid dendritic cells (PDC). By using virosomes containing encapsulated Melan-A peptide and a PDC line developed in our laboratory, we evaluated the response of Melan-A specific T cells. Virosomes have the capacity to bind PDC and are endocyted within vesicles in the cytosol. This endocytosis is inhibited by neuraminidase, suggesting that it is mediated by sialic acid present on cell surface. Furthermore, PDC loaded with Melan-A virosomes can induce a Melan-A specific T cell activation. Interestingly, they activate T cells with a better efficiency than PDC loaded with a free peptide and when PDC where previously activated by a TLR ligand. These results indicate that virosomes could be a suitable delivery system for tumor peptide in immunotherapy of cancer.

Domains: Immunology

Juliette Angel, Laurence Chaperot, Jean-Paul Molens, Paulette Mezin, Mario Amacker, et al.. Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells.. Vaccine, 2007, 25 (19), pp.3913-21. ⟨10.1016/j.vaccine.2007.01.101⟩. ⟨inserm-00261079⟩