Optimization of peptide-based cancer vaccine compositions, by sequential screening, using versatile liposomal platform.

Abstract

Therapeutic cancer vaccines need thoughtful design to efficiently deliver appropriate antigens and adjuvants to the immune system. In the current study, we took advantage of the versatility of a liposomal platform to conceive and customize vaccines containing three elements needed for the induction of efficient antitumor immunity: i) a CD4 epitope peptide able to activate CD4+ T helper cells, ii) a CD8 tumor-specific epitope peptide recognized by CD8+ T cytotoxic cells and iii) Pattern Recognition Receptor (PRR) agonists which stand as adjuvants. Each type of component, conjugated to liposomes, was evaluated individually by comparing their vaccine efficacy after immunization of naïve mice. These screening steps resulted in the optimization of three liposomal constructs bearing 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, which displayed antitumor efficiency against a mouse model of disseminated tumors transformed by HPV16. Our results validated the interest of our customizable liposomal platform as delivery system for cancer vaccination. We also demonstrated its interest as tool for vaccine design allowing the strategical selection of components, and the evaluation of epitope-adjuvant association.