A nano-liposome vaccine carrying E75, a HER-2/neu-derived peptide, exhibits significant antitumour activity in mice

Abstract

E75 (HER-2/neu-369–377), is an immunogenic peptide which is highly expressed in breast cancer patients. The purpose of this study was to develop an effective vaccine delivery/adjuvant system by attachment of this peptide to the surface of liposomes consisting of phospholipids including distearoylphosphocholine (DSPC) and distearoyl phosphoglycerol (DSPG) with high transition temperature (Tm) and dioleoylphosphatidylethanolamine (DOPE) (a pH-sensitive lipid for cytosolic antigen delivery) to improve antitumour immune activity against the E75 peptide. For this purpose, the E75 peptide was incorporated into liposomes consisting of DSPC/DSPG/cholesterol (Chol)/DOPE (15/2/3/5 molar ratio) through conjugation with distearoylphosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (maleimide-PEG₂₀₀₀-DSPE). Immunization of BALB/c mice was performed three times with different forms of liposomal formulations at 2-week intervals and antitumour immunity responses were evaluated. Results of ELISpot and flow cytometry analysis showed that mice vaccinated with DSPC/DSPG/Chol/DOPE/E75 have significantly enhanced the antigen-specific IFN-γ response of CD8⁺ T cells and generated cytotoxic T lymphocytes (CTL) antitumour responses. CTL responses induced by this formulation resulted in inhibition of tumour progression and longer survival time in the mice TUBO tumour model. The results revealed that the liposomes consist of DSPC/DSPG/Chol/DOPE could be suitable candidates for vaccine delivery of E75 peptide for the prevention and therapy of HER2-positive breast cancer and merit further investigation.

Keywords:

• Breast cancer
• E75 peptide
• HER2/neu
• phase transition temperature
• nano-liposome
• vaccine

Acknowledgements

This work was supported by Research Vice Chancellor and Research Council of Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. We would also like to thank Azam Abbasi and Zahra Saberi for their excellent technical assistance. This study was a part of A. Arab’s Ph.D dissertation.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by Research Vice Chancellor and Research Council of Mashhad University of Medical Sciences (MUMS), Mashhad, Iran [grant number: 922608].