Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide

Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide

^†Laboratory of Experimental Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, 2200N, Copenhagen, Denmark;^‡Departments of Oto-Rhino-Laryngology and ^¶Clinical Immunology, Rigshospital, University of Copenhagen, 2200N, Denmark; ^§Department of Tumor Cell Biology, The Danish Cancer Society, Copenhagen, 2100, Denmark; and ^‖Department of Immunohaematology and Blood Bank, University Hospital, Leiden, 2300RC, The Netherlands

Abstract

A cytotoxic T lymphocyte (CTL) clone generated in vitro from the peripheral blood of a healthy HLA-A2-positive individual against a synthetic p53 protein-derived wild-type peptide (L9V) was shown to kill squamous carcinoma cell lines derived from two head and neck carcinomas, which expressed mutant p53 genes, in a L9V/HLA-A2 specific and restricted fashion. Thus, the normal tolerance against endogenously processed p53 protein-derived self-epitopes can be broken by peptide-specific in vitro priming. p53 protein-derived wild-type peptides might thus represent tumor associated target molecules for immunotherapeutical approaches.

Footnotes

↵ ** To whom reprint requests should be addressed at: Department of Medical Anatomy, the Panum Institute, Blegdamsvej 3, 2200N, Copenhagen, Denmark.
Robert A. Good, University of South Florida, St. Petersburg, FL
Abbreviations: MHC, major histocompatibility complex; CTL, cytotoxic T lymphocyte; SCCHN, squamous cell carcinomas of head and neck; TNF, tumor necrosis factor.