The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2-restricted peptides and to induce strong antitumor 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-A10 _254-262- or MAGE-A3_271-279-derived peptides and to elicit potent specific CTL responses in vitro and in vivo. Interestingly, human anti-MAGE-A3_271-279-specific CTLs were able to kill human MAGE-A3⁺ tumor cells, even if these cells naturally express a low amount of MAGE-A3_271-279 peptide-HLA epitope surface complexes and are usually not recognized by CTLs generated by conventional stimulation procedures. MAGE-A3_271-279-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-D^b+) transgenic mice with phage particles expressing MAGE-A3_271-279-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.