Self-Assembling Peptide Epitopes As Novel Platform for Anticancer Vaccination Publisher Pubmed



Radmalekshahi M^{1, 3} ; Fransen MF² ; Krawczyk M¹ ; Mansourian M¹ ; Bourajjaj M¹ ; Chen J¹ ; Ossendorp F² ; Hennink WE¹ ; Mastrobattista E¹ ; Amidi M¹ Show Affiliations
Source: Molecular Pharmaceutics Published:2017

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. © 2017 American Chemical Society.