Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination
Author(s) -
Mazda RadMalekshahi,
Marieke F. Fransen,
Małgorzata Krawczyk,
Mercedeh Mansourian,
Meriem Bourajjaj,
Jian Chen,
Ferry Ossendorp,
Wim E. Hennink,
Enrico Mastrobattista,
Maryam Amidi
Publication year - 2017
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/acs.molpharmaceut.6b01003
Subject(s) - immunogenicity , epitope , peptide , antigen , nanocarriers , immune system , chemistry , peptide vaccine , virology , immunology , biology , biochemistry , drug delivery , organic chemistry
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 (OVA 250-264 , HPV-E7 43-57 ) 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 E7 43-57 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.
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