Antennapedia transduction sequence promotes anti tumour immunity to epicutaneously administered CTL epitopes.
The identification of tumor antigens has spurred the development of efficient adjuvants and novel delivery systems for cancer immunotherapy. To this end, a peptide-based vaccine consisting of the Antennapedia transduction sequence (ANTP) attached to an antigenic peptide was designed to enhance per-cutaneous delivery into cells of the epidermis and dermis. Here we show that the topical application of OVA(257-264) linked to ANTP in mice onto tape-stripped skin resulted in enhanced delivery of the antigen through the skin whereas OVA(257-264) alone remained distributed uniformly on the skin surface. This delivery correlated with an increase in the CTL response against OVA. When mixed with CpG oligodinucleotides (ODN), the recombinant antigen protected mice from tumor challenge. These data provide the first indication that in vivo use of a translocation sequence can enhance delivery of therapeutic peptides and increase anti-tumor immunity through a simple and safe mechanism involving enhanced penetration of the skin barrier.
Schutze-Redelmeier
Marie-Paule M
MP
Systemic Therapy Program, Advanced Therapeutics, British Columbia Cancer Research Centre, Vancouver, B.C, Canada.
Kong
Spencer
S
Bally
Marcel B
MB
Dutz
Jan P
JP
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000279:Administration, Cutaneous; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy*; D009841:Oligonucleotides / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012869:Skin Absorption; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014161:Transduction, Genetic
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D009841:Oligonucleotides; D007371:Interferon-gamma; D010047:Ovalbumin