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

Rossella Sartorius, Paola Pisu, Luciana D'Apice, Luciano Pizzella, Chiara Romano, Giancarlo Cortese, Angela Giorgini, Angela Santoni, Francesca Velotti, Piergiuseppe De Berardinis

Research output: Contribution to journalArticlepeer-review

Abstract

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-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.

Original languageEnglish
Pages (from-to)3719-3728
Number of pages10
JournalJournal of Immunology
Volume180
Issue number6
Publication statusPublished - Mar 15 2008

ASJC Scopus subject areas

  • Immunology

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