Identification of new antigenic peptide presented by HLA-Cw7 and encoded by several MAGE genes using dendritic cells transduced with lentiviruses.
Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because they are tumor specific and shared by tumors of different histological types. Several clinical trials are in progress with MAGE peptides, proteins, recombinant poxviruses, and dendritic cells (DC) pulsed with peptides or proteins. The use of gene-modified DC would offer the major advantage of a long-lasting expression of the transgene and a large array of antigenic peptides that fit into the different HLA molecules of the patient. In this study, we tested the ability of gene-modified DC to prime rare Ag-specific T cells, and we identified a new antigenic peptide of clinical interest. CD8(+) T lymphocytes from an individual without cancer were stimulated with monocyte-derived DC, which were infected with a second-generation lentiviral vector encoding MAGE-3. A CTL clone was isolated that recognized peptide EGDCAPEEK presented by HLA-Cw7 molecules, which are expressed by >40% of Caucasians. Interestingly, this new tumor-specific antigenic peptide corresponds to position 212-220 of MAGE-2, -3, -6, and -12. HLA-Cw7 tumor cell lines expressing one of these MAGE genes were lysed by the CTL, indicating that the peptide is efficiently processed in tumor cells and can therefore be used as target for antitumoral vaccination. The risk of tumor escape due to appearance of Ag-loss variants should be reduced by the fact that the peptide is encoded by several MAGE genes.
Breckpot
Karine
K
Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Brussels, Belgium.
Heirman
Carlo
C
De Greef
Catherine
C
van der Bruggen
Pierre
P
Thielemans
Kris
K
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015236:HLA-C Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D016086:Lentivirus / Q000235:genetics* / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods
D000951:Antigens, Neoplasm; D015236:HLA-C Antigens; C040178:HLA-C*70 antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010455:Peptides