Synthesis of lipo- and phospholipo- peptides to enhance cytotoxic t lymphocyte responses — ASN Events

Synthesis of lipo- and phospholipo- peptides to enhance cytotoxic t lymphocyte responses (#14)

Neil M O'Brien-Simpson 1 , Jason Lenzo 1 , Troy J Attard 1 , Eric C Reynolds 1
  1. University of Melbourne, Carlton, VIC, Australia

Cytotoxic T lymphocytes (CTL) have a major immunological role in the clearance of viral infected cells and have been shown to highly effective against cancer cells. CTL’s recognise linear 8-11mer peptides (CTL epitope) bound to major histocompatibility complex (MHC) class I and presented by antigen presenting cells. Once activated, CTL’s are then able to kill viral infected cells or cancer cells that display the relevant CTL epitope. The ability of CTL’s to recognise small linear peptides has resulted considerable research into developing CTL based vaccine strategies and therapies, however a number of issues centered on stimulating a strong and long lasting immune response has hampered development. The incorporation of lipid moieties into peptide based vaccines has been shown to enhance antibody and cellular responses. Here we have synthesized di-palmitoyl CTL epitope based immunogens to investigate enhancing the immune response to the tumor antigen survivin. In an attempt to further enhance the immune response we synthesized di-palmitoyl CTL immunogen analogues to incorporate a promiscuous helper T lymphocyte epitope from tetanus toxoid, diamino butyric acid and phosphoseryl residues to mimic bacterial and phospholipid moieties known to be immunostimulatory. The effect of each of the di-palmitoyl CTL immunogens was evaluated using an in-vivo CTL killing model and ex-vivo assays against survivin expressing cell lines. Further the ability of each immunogen to enhance the immune response was evaluated using proliferation, ELISPOT and cytokine assays.