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Merck
CN
  • MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer.

MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer.

Journal of controlled release : official journal of the Controlled Release Society (2019-04-19)
Parvin Zamani, Jamshid Gholizadeh Navashenaq, Amin Reza Nikpoor, Mahdi Hatamipour, Reza Kazemi Oskuee, Ali Badiee, Mahmoud Reza Jaafari
摘要

Liposomal peptide-based vaccines can potentially suppress cancer cells proliferation in the host. To enhance the effectiveness of vaccination against cancer, additional strategies should also be employed. One strategy to promote peptide-based vaccine efficacy and induce powerful immune responses, is simultaneous activation of CD4+ and CD8+ T cells. To address this problem, we tested the efficacy of a nano-liposomal vaccine containing P5 peptide, a cytotoxic T lymphocytes (CTL) specific peptide derivative of rat HER2/neu protein, Pan HLA-DR (PADRE) peptide, a universal CD4+ T helper cell epitope and monophosphoryl lipid A (MPL) a toll-like receptor 4 ligand. We observed potent CD8+ T cell immune responses in TUBO mice vaccinated with liposomal P5 peptide in combination with PADRE and MPL. Also, this formulation remarkably improved anti-tumor effects against cells overexpressing HER2 in BALB/c mice compared to liposomal vaccine containing P5 only. Furthermore, we found that vaccination with Lip-P5- Integrated PADRE-MPL formulation significantly induced IFN-γ production, increased CD8+ T cells numbers and enhanced survival compared to other groups of treated mice. In conclusion, our study indicated that Lip-P5-Integrated PADRE-MPL, after further confirmatory investigations, could be employed as a promising vaccine to generate potent CTL anti-tumor immune responses that could be beneficial to treatment of HER2+ breast cancer.