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

Abstract

Delivery of tumor-associated antigen (TAA)-derived peptides in a high immunogenic form represents one of the key issues for effective peptide-based cancer vaccine development. Here, we report the ability of non-pathogenic filamentous bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10254-262- or MAGE-A3271-279-derived peptides and 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 antigen 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 TAA-derived peptides, thus representing a novel powerful system for the development of effective peptide-based cancer vaccines.