The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/695/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 5, August 29, 1997 695-704

Article

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

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

From the * Department of Immunohematology and Blood Bank, University Hospital Leiden, 2300 RC Leiden, the Netherlands; {ddagger} 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-2Kb, 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.

Address correspondence to Cornelis J.M. Melief, Department of Immunohematology and Blood Bank, University Hospital Leiden, Bldg, 1, E3-Q, PO box 9600, 2300 RC Leiden, The Netherlands. Phone: 31-71-5263800; FAX: 31-71-5216751.

H.W. Nijman was supported by The Netherlands Organization for Scientific Research grant 900-716-075.

1 Abbreviations used in this paper: aa, amino acids; FLVenv, Friend leukemia virus envelope; MEC, mouse embryo cell; wt, wild type.

M.P.M. Vierboom and H.W. Nijman contributed equally to this paper.


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