Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination.

Abstract

The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA250-264, HPV-E743-57) to generate self-assembling peptide epitopes (SAPEs). The obtained results showed that the SAPEs were able to form nanostructures with a diameter from 20 to 200 nm. The SAPEs adjuvanted with CpG induced and expanded antigen-specific CD8+ T cells in mice. Furthermore, tumor-bearing mice vaccinated with SAPEs harboring the HPV E743-57 peptide showed a delayed tumor growth and an increased survival compared to sham-treated mice. In conclusion, self-assembling peptide based systems increase the immunogenicity of peptide epitope vaccines and therefore warrants further development toward clinical use.

• Authors: Mazda Rad-Malekshahi, Marieke F Fransen, Małgorzata Krawczyk, Mercedeh Mansourian, Meriem Bourajjaj, Jian Chen, Ferry Ossendorp, Wim E Hennink, Enrico Mastrobattista, Maryam Amidi
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 14 Issue 5 Pg. 1482-1493 (05 01 2017) ISSN: 1543-8392 [Electronic] United States
• PMID: 28088862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Peptides
• Ovalbumin

Topics

• Animals
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Cancer Vaccines (immunology, metabolism)
• Cells, Cultured
• Epitopes, T-Lymphocyte (immunology, metabolism)
• Immunotherapy
• Mice
• Nanoparticles (chemistry)
• Ovalbumin (chemistry)
• Peptides (immunology)
• Vaccination (methods)