Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination

Mazda Rad-Malekshahi, Marieke F. Fransen, Małgorzata Krawczyk, Mercedeh Mansourian, Meriem Bourajjaj, Jian Chen, Ferry Ossendorp, Wim E. Hennink, Enrico Mastrobattista, Maryam Amidi

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)1482-1493
JournalMolecular Pharmaceutics
Volume14
Issue number5
DOIs
Publication statusPublished - 2017
Externally publishedYes

Cite this

Rad-Malekshahi, M., Fransen, M. F., Krawczyk, M., Mansourian, M., Bourajjaj, M., Chen, J., ... Amidi, M. (2017). Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination. Molecular Pharmaceutics, 14(5), 1482-1493. https://doi.org/10.1021/acs.molpharmaceut.6b01003