The DAM gene family encodes a new group of tumor-specific antigens recognized by human leukocyte antigen A2-restricted cytotoxic T lymphocytes.
The DAM family of genes has a high degree of homology with MAGE, both in nucleotide sequence and in neoplastic tissue-specific expression. This study describes, for the first time, the identification of CTLs specific for a peptide epitope encoded by DAM genes. A human leukocyte antigen (HLA)-A2-restricted CTL clone was raised against a peptide, D10/6-271, encoded by codons 271-279 in the DAM cDNA. The corresponding peptide in the MAGE-3 sequence, M3-271, has been shown previously to be a natural T-cell epitope for HLA-A2-restricted CTLs recognizing the MAGE-3 protein. The D10/6-271-specific CTL clone required approximately 3 nM exogenous peptide for half-maximal lysis of target cells and was able to specifically recognize endogenous DAM antigen on HLA-A2+ melanoma cells infected with a vaccinia vector recombinant for gene DAM-6. These data suggest that DAM genes might encode a new group of tumor-specific antigens useful for the design of specific antitumor vaccines.
Telethon Institute of Gene Therapy, Istituto Scientifico H. S. Raffaele, Milan, Italy. fleisck@tigem.it
K
K
Fleischhauer
L
L
Gattinoni
P
P
Dalerba
G
G
Lauvau
E
E
Zanaria
B
B
Dabovic
P M
PM
van Endert
C
C
Bordignon
C
C
Traversari
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000628:therapy; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D015789:HLA-A2 Antigen; C072012:MAGEB2 protein, human; D009363:Neoplasm Proteins; D010455:Peptides