Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 productby DNA vaccination

We recently have reported that Wilms' tumor gene WT1 is highly expressed no t only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTL s) can be elicited by immunization with 9-mer WT1 peptides capable of bindi ng to major histocompatibility complex (MHC) class I molecules. In the pres ent study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmi d DNA elicited CTLs against the WT1 protein, and the CTLs specifically kill ed WT1-expressing tumor cells in a MHC class I-restricted manner. Furthermo re, the vaccinated mice rejected the challenges of WT1-expressing tumor cel ls and survived with no signs of autoimmunity caused by the CTLs. These res ults demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rej ection activity against challenges of WT1-expressing tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid tu mors as well as leukemias.