Patients with various solid tumors develop antibodies against the growth suppressor protein p53. The percentage of positive sera for patients with colon cancer varied over a wide range, which might be due to the different methods or the different antigens, which were used for the detection of p53 autoantibodies. We analyzed sera from patients with diagnosed colon cancer by ELISA using native p53 from a tumor cell line as well as by Western blotting with full-length or C- or N-terminal fragments of p53. Finally, sera were analyzed with a peptide library consisting of 16-amino-acid peptides, which cover the entire p53 sequence. By using these different methods we found 7 out of 127 sera (5.5%) to be positive for p53 autoantibodies. Two antibodies out of 7 reacted only with epitopes in the N-terminus whereas 5 sera reacted with N- and C-terminal sequences. All of these sera recognized common epitopes, which are also detected by a number of mouse monoclonal antibodies indicating immune-dominant epitopes for mouse and man on the polypeptide chain of p53. The sequences of these epitopes might be useful for the treatment of tumor patients either by neutralizing p53 autoantibodies or for vaccination.

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