Induction of MAGE Genes in Lymphoid Cells by the Demethylating Agent 5‐Aza‐2′‐deoxycytidine

MAGE genes encoding tumor antigens recognized by cytotoxic T lymphocytes are appropriate target molecules for specific immunotherapy of cancer. We have investigated whether the demethylating agent 5‐aza‐2′‐deoxycytidine (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 MAGE‐1 in IL‐2‐dependent T cell clones and all MAGE genes tested in Epstein‐Barr virus‐transformed B cell lines. Expression of MAGE‐1 protein in the cells was confirmed 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.