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

• DOI: 10.1084/jem.186.5.695
• Publication Date: 2002-07-26T16:49:30Z
• Authors: Michel P.M. Vierboom; Hans W. Nijman; Rienk Offringa; Ellen I.H. van de...; Thorbald van Hall; Lambert van den B...; Gert Jan Fleuren; Peter Kenemans; W. Martin Kast; Cornelis J.M. Melief
• Keywords: Mice, Knockout; Cell Survival; Histocytochemistry; H-2 Antigens; Mice, Nude; Neoplasms, Experimental; Adoptive Transfer; Peptide Fragments; Clone Cells; 3. Good health; Mice, Inbred C57BL; Epitopes; Mice; 03 medical and health sciences; 0302 clinical medicine; Tumor Cells, Cultured; Animals; Immunization; Immunotherapy; Tumor Suppressor Protein p53; T-Lymphocytes, Cytotoxic

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