TUMOR-ERADICATION BY WILD-TYPE P53-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

The tumor suppressor protein p53 is overexpressed in close to 50% of a ll human malignancies. The p53 protein is therefore an attractive targ et for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a mur ine wild-type p53 peptide, presented by the major histocompatibility c omplex class I molecule H-2K(b), were generated by immunizing p53 gene deficient (p53 -/-) C57BL/6 mice with syngeneic p53-overexpressing tu mor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/nude mice caused complete and permanent tumor eradication. Importantly , this occurred in the absence of any demonstrable damage to normal ti ssue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were ca pable of preventing tumor outgrowth. Wild-type p53-specific CTLs can a pparently discriminate between p53-overexpressing tumor cells and norm al tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.