Antennapedia transduction sequence promotes anti tumour immunity to epicutaneously administered CTL epitopes

Abstract

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.