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Molecules 2018, 23(9), 2233; https://doi.org/10.3390/molecules23092233

Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope

1
School of Medical Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia
2
Bio-Organic and Medicinal Chemistry Laboratory, Burnet Institute, 85 Commercial Rd, Melbourne 3004, Australia
3
Dendritic Cell Biology and Therapeutics Group, ANZAC Medical Research Institute, Institute of Haematology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia
4
Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia
5
Department of Immunology, Monash University, Clayton, Victoria 3800, Australia
6
Baker Heart and Diabetes Institute, Melbourne 3004, Australia
7
College of Health and Biomedicine, Victoria University, Melbourne 3021, Australia
These authors contributed equally.
*
Author to whom correspondence should be addressed.
Academic Editor: Rakesh K. Tiwari
Received: 15 August 2018 / Revised: 29 August 2018 / Accepted: 30 August 2018 / Published: 2 September 2018
(This article belongs to the Special Issue Cell-Penetrating Peptides (CPPs))
Full-Text   |   PDF [4424 KB, uploaded 2 September 2018]   |  

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. View Full-Text
Keywords: penetratin; membrane translocating peptide; membrane penetrating peptide; vaccine; Mucin 1; immunogenicity; antigen delivery; immunotherapy; multiple antigen peptide; TLR agonist penetratin; membrane translocating peptide; membrane penetrating peptide; vaccine; Mucin 1; immunogenicity; antigen delivery; immunotherapy; multiple antigen peptide; TLR agonist
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Brooks, N.; Hsu, J.; Esparon, S.; Pouniotis, D.; Pietersz, G.A. Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope. Molecules 2018, 23, 2233.

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