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Mol Pharm. 2017 May 1;14(5):1482-1493. doi: 10.1021/acs.molpharmaceut.6b01003. Epub 2017 Jan 27.

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

Author information

1
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.
2
Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.
3
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, The Netherlands.

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.

KEYWORDS:

human papillomavirus (HPV); immunotherapy; nanoparticles; ovalbumin (OVA); self-assembling peptide epitopes; therapeutic cancer vaccine

PMID:
28088862
PMCID:
PMC5415879
DOI:
10.1021/acs.molpharmaceut.6b01003
[Indexed for MEDLINE]
Free PMC Article

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