Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists.
Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which leads to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8+ T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of vaccines.
['Jacoberger-Foissac|Célia|C|', 'Saliba|Hanadi|H|', 'Wantz|May|M|', 'Seguin|Cendrine|C|', 'Flacher|Vincent|V|', 'Frisch|Benoît|B|', 'Heurtault|Béatrice|B|', 'Fournel|Sylvie|S|']
D056704:Adaptive Immunity D000818:Animals D000970:Antineoplastic Agents D018414:CD8-Positive T-Lymphocytes D019496:Cancer Vaccines D045744:Cell Line, Tumor D049109:Cell Proliferation D008081:Liposomes D008175:Lung Neoplasms D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D000070576:NLR Proteins D010455:Peptides D051193:Toll-Like Receptors
Delivery system HPV-transformed pulmonary tumors Liposomal nanoparticles Therapeutic vaccines Toll-like and nod-like receptor agonists