INDUCTION OF MAGE GENES IN LYMPHOID-CELLS BY THE DEMETHYLATING AGENT 5-AZA-2'-DEOXYCYTIDINE

MAGE genes encoding tumor antigens recognized by cytotoxic T lymphocyt es are appropriate target molecules for specific immunotherapy of canc er. We have investigated whether the demethylating agent 5-aza-2'-deox ycytidine (DAC) induces MAGE-1, -2 -3, and -6 in normal and malignant lymphoid cells. DAC induced these MAGE genes in both PHA/interleukin-2 (IL-2)-activated T cells from healthy donors and MAGE-negative T and B cell leukemias in most cases. It also induced IMAGE-I in IL-2-depend ent T cell clones and all MAGE genes tested in Epstein-Barr virus-tran sformed B cell lines. Expression of MAGE-1 protein in the cells was co nfirmed by western blot analysis with anti-MAGE-1 polyclonal antibody. Therefore, demethylation is a potent stimulus to induce MAGE genes in both normal and malignant lymphoid cells.