The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2 restricted peptides and to induce strong anti-tumor CTL responses

Delivery of tumor-associated Ag-derived peptides in a high immunogenic form represents one of the key issues for effective peptide-based cancer vaccine development. We report herein the ability of nonpathogenic filamentous bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10254–262- or MAGE-A3271–279-derived peptides and to elicit potent specific CTL responses in vitro and in vivo. Interestingly, human anti-MAGE-A3271–279-specific CTLs were able to kill human MAGE-A3_ tumor cells, even if these cells naturally express a low amount of MAGE-A3271–279 peptide-HLA epitope surface complexes and are usually not recognized by CTLs generated by conventional stimulation procedures. MAGE-A3271–279-specific/CD8_ CTL clones were isolated from in vitro cultures, and their high avidity for Ag recognition was assessed. Moreover, in vivo tumor protection assay showed that vaccination of humanized HHD (HLA-A2.1_/H2-Db_) transgenic mice with phage particles expressing MAGE-A3271–279-derived peptides hampered tumor growth. Overall, these data indicate that engineered filamentous bacteriophage virions increase substantially the immunogenicity of delivered tumor-associated Ag-derived peptides, thus representing a novel powerful system for the development of effective peptide-based cancer vaccines.