title: Comparative Immunogenicity of a Cytotoxic T Cell Epitope Delivered by Penetratin and TAT Cell Penetrating Peptides.
abstract: 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.
authors.affiliation: School of Medical Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia. brooksy_4567@hotmail.com.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brooks
authors.affiliation: Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne 3004, Australia. sesparon@burnet.edu.au.
authors.forename: Sandra
authors.initials: S
authors.lastname: Esparon
authors.affiliation: School of Medical Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia. dodie.pouniotis@rmit.edu.au.
authors.forename: Dodie
authors.initials: D
authors.lastname: Pouniotis
authors.affiliation: Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne 3004, Australia. gpietersz@burnet.edu.au.|Department of Pathology, University of Melbourne, Parkville 3010, Victoria, Australia. gpietersz@burnet.edu.au.|Department of Immunology, Monash University, Clayton 3800, Victoria, Australia. gpietersz@burnet.edu.au.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Pietersz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018984:Epitopes, T-Lymphocyte; D018396:Mucin-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D010047:Ovalbumin; C414409:penetratin
keywords: CPP; TAT; antigen delivery; antigen presentation; cytotoxic T cell epitope; immunogenicity; immunotherapy; membrane penetrating peptide; membrane translocating peptide; penetratin; vaccine