Abstract
Peptide-based vaccines for cancer have many advantages however, for optimization these immunogens should incorporate peptide epitopes that induce CD8, as well as CD4 responses, antibody and long term immunity. Cell penetrating peptides (CPP) with a capacity of cytosolic delivery have been used to deliver antigenic peptides and proteins to antigen presenting cells to induce cytotoxic T cell, helper T cell and humoral responses in mice. For this study, a tripartite CPP including a mucin 1 (MUC1) variable number of tandem repeat (VNTR) containing multiple T cell epitopes and tetanus toxoid universal T helper epitope peptide (tetCD4) was synthesised (AntpMAPMUC1tet) and immune responses investigated in mice. Mice vaccinated with AntpMAPMUC1tet + CpG show enhanced antigen-specific interferon-gamma (IFN-γ) and IL-4 T cell responses compared with AntpMAPMUC1tet vaccination alone and induced a Th1 response, characterised by a higher ratio of IgG2a antibody/IgG1 antibodies. Furthermore, vaccination generated long term MUC1-specific antibody and T cell responses and delayed growth of MUC1+ve tumours in mice. This data demonstrates the efficient delivery of branched multiple antigen peptides incorporating CPP and that the addition of CpG augments immune responses.
Highlights
Despite encouraging results in some clinical trials, cancer vaccines are yet to have an impact on cancer [1,2]
Mucin 1 (MUC1), is a type I transmembrane glycoprotein with a protein core consisting of a 20 amino acid variable number of tandem repeat (VNTR) region (PGSTAPPAHGVTSAPDTRPA), which is frequently over-expressed by adenocarcinoma cells at levels
Cell penetrating peptides (CPP) peptides chemically conjugated to protein antigens or linear synthetic peptides of CPP fused in tandem with cytotoxic (Tc) or helper (Th) T cell epitopes have been used
Summary
Despite encouraging results in some clinical trials, cancer vaccines are yet to have an impact on cancer [1,2]. The cell penetrating property of these peptides have been utilized to deliver antigenic peptide and proteins into any antigen presenting cell including DCs for the development of vaccine delivery systems [4,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39] For this purpose, CPP peptides chemically conjugated to protein antigens or linear synthetic peptides of CPP fused in tandem with cytotoxic (Tc) or helper (Th) T cell epitopes have been used. Long term MUC1-specific antibody and T cell responses were generated by the tripartite peptide
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