Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists.
Fiche publication
Date publication
mai 2020
Journal
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FOURNEL Sylvie, Dr FRISCH Benoit, Dr HEURTAULT Béatrice, Dr FLACHER Vincent
Tous les auteurs :
Jacoberger-Foissac C, Saliba H, Wantz M, Seguin C, Flacher V, Frisch B, Heurtault B, Fournel S
Lien Pubmed
Résumé
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 lead 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.
Mots clés
Delivery system, HPV-transformed pulmonary tumors, Liposomal nanoparticles, Therapeutic vaccines, Toll-like and nod-like receptor agonists
Référence
Eur J Pharm Biopharm. 2020 May 29;: