Efficient delivery of antennapedia homeodomain fused to CTL epitope with liposomes into dendritic cells results in the activation of CD8(+) T cells

The in vivo induction of a CTL response using Antennapedia homeodomain (Ant pHD) fused to a poorly immunogenic CTL epitope requires that the Ag is give n in presence of SDS, an unacceptable adjuvant for human use. In the presen t report, we developed a hybrid CTL epitope delivery system consisting of A ntpHD peptide vector formulated in liposomes as an alternative approach to bypass the need for SDS. It is proposed that liposomes will prevent degrada tion of the Ag in vivo and will deliver AntpHD recombinant peptide to the c ytosol of APCs. We show in this work that dendritic cells incubated with An tpHD-fused peptide in liposomes can present MHC class I-restricted peptide and induce CTL response with a minimal amount of Ag. Intracellular processi ng studies have shown that encapsulated AntpHD recombinant peptide is endoc ytized before entering the cytosol, where it is processed by the proteasome complex. The processed liposomal peptides are then transported to the endo plasmic reticulum. The increase of the CTL response induced by AntpHD-fused peptide in liposomes correlates with this active transport to the class I- processing pathway. In vivo studies demonstrated that positively charged li posomes increase the immunogenicity of AntpHD-Cw3 when injected s.c. in mic e in comparison to SDS. Moreover, addition of CpG oligodeoxynucleotide immu nostimulatory sequences further increase the CD8(+) T cell response. This s trategy combining lipid-based carriers with AntpHD peptide to target poorly immunogenic Ags into the MHC class I processing pathway represents a novel approach for CTL vaccines that may have important applications for develop ment of cancer vaccines.