Nanoliposomal vaccine containing long multi-epitope peptide E75-AE36 pulsed PADRE-induced effective immune response in mice TUBO model of breast cancer

Abstract

The main goal of peptide-based cancer vaccines is to induce the immune system and activation of effective T cell responses against cancerous cells. Nevertheless, the potency of peptide vaccines is insufficient in most of cases and had limited clinical success. Therefore, the optimization of peptide-based cancer vaccine is essential to achieve powerful therapeutic outcomes. One strategy to enhanced potency of peptide vaccines and induce strong immune responses is the preparation of multi-epitope peptide formulation containing both Th- and cytotoxic T lymphocyte–induced responses epitope using suitable delivery system. For this reason, we studied the effect of Dioleoylphosphatidylethanolamine-containing liposomal vaccine composed of a mixture of short peptides AE36 and E75 (HER2/neu-derived peptides) and long multi-epitope peptide E75-AE36 (linkage of short peptides) in combination with a Pan HLA-DR epitope (PADRE) peptide. These formulations were examined using a series of subcutaneously injection to HER-2+ TUBO-tumoured mice in prophylactic and therapeutic model. We observed that mice vaccinated with liposomal long peptide in combination with PADRE resulted in the superior induction of CD4+ and CD8+ T cells responses and significantly enhanced production of IFN-γ compared with liposomal short peptides and non-liposomal peptides formulations. Moreover, liposome-long peptide with PADRE led to the considerable reduction of tumour growth and lifespan induction in mouse model. In conclusion, our study indicated that liposomal formulation containing long multi-epitope peptide E75-AE36 with PADRE could be used as an effective multi-epitope prophylactic/therapeutic vaccine to generate potent antigen-specific CD8+ T-cell immune response and may be introduced as a possible candidate peptide vaccine for breast cancer.