Review Article WT1 (Wilms ’ Tumor Gene 1): Biology and Cancer Immunotherapy

Wilms ’ tumor gene WT1 encodes a transcription factor and plays an important role in cell growth and differentiation. The WT1 gene is highly expressed in leukemia and various types of solid tumors, whereas WT1 is a tumor marker convenient for the detection of minimal residual disease of leukemia. The WT1 gene was originally defined as a tumor suppressor gene, but we proposed that it was, on the contrary, an oncogene. Furthermore, the WT1 protein has proven to be a promising tumor-associated antigen, in which many human leukocyte antigen class I- or II-restricted WT1 epitopes have been identified. Clinical trials of WT1-targeted immu-notherapy have confirmed its safety and clinical efficacy. WT1-specific cytotoxic T lymphocytes and WT1 antibodies are spontaneously induced in tumor-bearing patients, probably because of high immunogenicity of the WT1 protein. WT1-specific cytotoxic T lymphocytes make a major contribution to the graft-versus-leukemia effect after allogenic stem cell transplantation. When 75 cancer antigens including WT1 were prioritized according to several criteria such as thera-peutic function and immunogenicity, WT1 was ranked as the top antigen. These findings suggest that a new era of WT1 immunotherapy is imminent