Cancer immunotherapy targeting Wilms’ tumor gene WT1 product

Abstract

The Wilms’ tumor gene WT1 is expressed at high levels in leukemic blast cells in most acute myeloid and lymphoblastic leukemias. In myelodysplastic syndrome, WT1 mRNA expression levels increase along with disease progression; thus, WT1 mRNA is a tumor marker for leukemic blast cells. WT mRNA is also expressed at high levels in various types of solid cancers, including cancers of the lung, breast, colon and pancreas. Patients with WT1-expressing tumors produce antibodies and cytotoxic T-lymphocytes against WT1 protein, indicating that WT1 protein is highly immunogenic and a promising tumor antigen. Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte and class II-restricted helper epitopes of WT1 protein were identified, and clinical studies of cancer immunotherapy using these cytotoxic T-lymphocyte epitope peptides were performed without significant adverse effect and with clinical results promising enough to encourage further clinical trials. The clinical efficacy of cancer immunotherapy targeting the WT1 protein should be clarified by a large-scale clinical study.

Keywords::

• cancer immunotherapy
• tumor marker
• Wilms’ tumor gene
• WT1