J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/695/10 $2.00
Volume 186, Number 5, August 29, 1997 695-704

Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes

By Michel P.M. Vierboom,^* Hans W. Nijman,^* Rienk Offringa,^* Ellen I.H. van der Voort,^* Thorbald van Hall,^* Lambert van den Broek,^§ Gert Jan Fleuren,^§ Peter Kenemans, W. Martin Kast, and Cornelis J.M. Melief^*

From the ^* Department of Immunohematology and Blood Bank, University Hospital Leiden, 2300 RC Leiden, the Netherlands;  Department of Obstetrics and Gynaecology, Free University Hospital, 1007 MB Amsterdam, The Netherlands; ^§ Department of Pathology, University Hospital Leiden, 2300 RC Leiden, The Netherlands; and  Cancer Immunology Program, Cardinal Bernadin Cancer Center, Loyola University of Chicago, Maywood, Illinois 60153

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2K^b, were generated by immunizing p53 gene deficient (p53 /) C57BL/6 mice with syngeneic p53-overexpressing tumor 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 tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.

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