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.
Sartorius
Rossella
R
Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Naples, Italy.
Pisu
Paola
P
D'Apice
Luciana
L
Pizzella
Luciano
L
Romano
Chiara
C
Cortese
Giancarlo
G
Giorgini
Angela
A
Santoni
Angela
A
Velotti
Francesca
F
De Berardinis
Piergiuseppe
P
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017104:Bacteriophage M13 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005818:Genetic Engineering; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens; C121012:MAGEA10 protein, human; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments