A simple but effective cancer vaccine consisting of an antigen and a cationic lipid |
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Authors: | Weihsu Chen Weili Yan Leaf Huang |
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Institution: | (1) Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, 2316 Kerr Hall, CB# 7360, Chapel Hill, NC 27599, USA;(2) Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15260, USA |
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Abstract: | Developing a cancer vaccine with a potent adjuvant, which is safe for human use, remains to be an unmet need. In this study,
we developed a simple, safe, yet efficient, peptide-based therapeutic cancer vaccine, DOTAP/E7 complex, which comprises only
two molecules: a DOTAP cationic lipid and a peptide antigen derived from E7 oncoprotein of human papillomavirus (HPV) type
16. The anti-cancer activity of DOTAP/E7 against existing HPV positive TC-1 tumor was compared to that of our previous LPD/E7
formulation, which contains bacterial DNA CpG motifs. Tumor-bearing mice showed significant tumor inhibition following a single
vaccination of either formulation at the optimal lipid dose, suggesting that DOTAP liposome alone can provide a potent adjuvant
activity without plasmid DNA. E7 peptide formulated with DOTAP induced migration of activated dendritic cells (DC) to the
draining lymph node (DLN) and efficiently generated functional antigen-specific CD8+ T lymphocyte responses. Accumulation of CD8+ tumor infiltrating T cells and apoptosis at tumor sites were observed after treatment with DOTAP/E7 complexes, which was
also associated with a decreased amount of CD25+Foxp3+ regulatory T cells in treated animals. Reactive oxygen species (ROS) induced by DOTAP cationic lipid in DLN revealed a plausible
mechanism of the initial interaction between DC and DOTAP. An adequate amount of ROS generation was apparently required for
the initiation of the vaccine mechanism; however, an overdose of DOTAP induced massive ROS production and apoptosis of DC
in DLN, which led to diminished anti-cancer immunity. Overall, these results indicate that cationic lipid DOTAP alone serves
as an efficient vaccine adjuvant for the induction of a therapeutic, antigen-specific anti-cancer activity. |
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Keywords: | Cancer immunotherapy Cationic liposomes Cervical cancer CTL ROS Vaccine adjuvant |
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