The Use of Filamentous Bacteriophagefdto Deliver MAGE-A10 or MAGE-A3 HLA-A2-Restricted Peptides and to Induce Strong Antitumor CTL Responses

• DOI: 10.4049/jimmunol.180.6.3719
• Publication Date: 2014-04-18T23:47:10Z
• Authors: Rossella Sartorius; Paola Pisu; Luciana D’Apice; Luciano Pizzella; Chiara Romano; Giancarlo Cortese; Angela Giorgini; Angela Santoni; Francesca Velotti; Piergiuseppe De B...
• Keywords: CTL*; Avidity; Cancer Immunotherapy

Abstract Delivery of tumor-associated Ag-derived peptides in a high immunogenic form represents one the key issues for effective peptide-based cancer vaccine development. We report herein ability nonpathogenic filamentous bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10254–262- or MAGE-A3271–279-derived and elicit potent specific CTL responses vitro vivo. Interestingly, human anti-MAGE-A3271–279-specific CTLs were able kill MAGE-A3+ tumor cells, even if these cells naturally express low amount MAGE-A3271–279 peptide-HLA epitope surface complexes are usually not recognized by generated conventional stimulation procedures. MAGE-A3271–279-specific/CD8+ clones isolated from cultures, their avidity Ag recognition was assessed. Moreover, vivo protection assay showed that vaccination humanized HHD (HLA-A2.1+/H2-Db+) transgenic mice with phage particles expressing hampered growth. Overall, data indicate engineered increase substantially immunogenicity delivered peptides, thus representing novel powerful system development vaccines.