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Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
Open AccessArticle

Comparative Immunogenicity of a Cytotoxic T Cell Epitope Delivered by Penetratin and TAT Cell Penetrating Peptides

1
School of Medical Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia
2
Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne 3004, Australia
3
Department of Pathology, University of Melbourne, Parkville 3010, Victoria, Australia
4
Department of Immunology, Monash University, Clayton 3800, Victoria, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Derek J. McPhee
Molecules 2015, 20(8), 14033-14050; https://doi.org/10.3390/molecules200814033
Received: 1 May 2015 / Revised: 16 July 2015 / Accepted: 29 July 2015 / Published: 3 August 2015
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
Cell penetrating peptides (CPP), including the TAT peptide from the human immunodeficiency virus transactivator of transcription (HIV-TAT) protein and penetratin from Drosophila Antennapedia homeodomain protein, translocate various cargos including peptides and proteins across cellular barriers. This mode of delivery has been harnessed by our group and others to deliver antigenic proteins or peptides into the cytoplasm of antigen processing cells (APC) such as monocyte-derived dendritic cells (MoDC). Antigens or T cell epitopes delivered by CPP into APC in vivo generate antigen-specific cytotoxic T cell and helper T cell responses in mice. Furthermore, mice immunised with these peptides or proteins are protected from a tumour challenge. The functional properties of CPP are dependent on the various cargos being delivered and the target cell type. Despite several studies demonstrating superior immunogenicity of TAT and Antp-based immunogens, none has compared the immunogenicity of antigens delivered by TAT and Antp CPP. In the current study we demonstrate that a cytotoxic T cell epitope from the mucin 1 (MUC1) tumour associated antigen, when delivered by TAT or Antp, generates identical immune responses in mice resulting in specific MUC1 T cell responses as measured by in vivo CTL assays, IFNγ ELISpot assays and prophylactic tumour protection. View Full-Text
Keywords: TAT; penetratin; CPP; membrane translocating peptide; membrane penetrating peptide; vaccine; cytotoxic T cell epitope; immunogenicity; antigen presentation; antigen delivery; immunotherapy TAT; penetratin; CPP; membrane translocating peptide; membrane penetrating peptide; vaccine; cytotoxic T cell epitope; immunogenicity; antigen presentation; antigen delivery; immunotherapy
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Brooks, N.; Esparon, S.; Pouniotis, D.; Pietersz, G.A. Comparative Immunogenicity of a Cytotoxic T Cell Epitope Delivered by Penetratin and TAT Cell Penetrating Peptides. Molecules 2015, 20, 14033-14050.

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