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The DAM Gene Family Encodes a New Group of Tumor-specific Antigens Recognized by Human Leukocyte Antigen A2-restricted Cytotoxic T Lymphocytes¹

Telethon Institute of Gene Therapy, Istituto Scientifico H. S. Raffaele, I-20132 Milan, Italy [K. F., L. G., P. D., C. B., C. T.]; Institut National de la Santé et de la Recherche Medicale, Unité 25, 7-75743 Paris, France [G. L., P. M. v. E.]; and Biologia Generale e Genetica Medica, Università di Pavia, I-27100 Pavia, Italy [E. Z., B. D.]

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 recognized 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.

¹ This work was supported in part by grants from the Italian Association for Cancer Research (Milan, Italy), from the National Research Council (CNR), Special Project "ACRO," and from the European Community, Biomed2 Program (BMH4-CT95-1627), and by Boehringer Mannheim (Penzberg, Germany).

² To whom requests for reprints should be addressed, at Telethon Institute of Gene Therapy, DIBIT-Istituto Scientifico H.S. Raffaele, via Olgettina 58, I-20132 Milan, Italy. Phone: 0039-2-2643-4708; Fax: 0039-2-2643-4827; E-mail: fleisck@tigem.it.

Received 5/ 8/98. Accepted 6/ 1/98.

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