TY - JOUR
T1 - Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination
AU - Radmalekshahi, Mazda
AU - Fransen, Marieke F
AU - Krawczyk, Małgorzata
AU - Mansourian, Mersedeh
AU - Bourajjaj, Meriem
AU - Chen, Jian
AU - Ossendorp, Ferry
AU - Hennink, Wim E
AU - Mastrobattista, Enrico
AU - Amidi, Maryam
PY - 2017/1/27
Y1 - 2017/1/27
N2 - 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.
AB - 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.
KW - therapeutic cancer vaccine
KW - immunotherapy
KW - human papillomavirus (HPV)
KW - ovalbumin (OVA)
KW - self-assembling peptide epitopes
KW - nanoparticles
U2 - 10.1021/acs.molpharmaceut.6b01003
DO - 10.1021/acs.molpharmaceut.6b01003
M3 - Article
C2 - 28088862
SN - 1543-8384
VL - 14
SP - 1482
EP - 1493
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
ER -