Dendritic cells transduced with full-length wild-type p53 generate antitumor cytotoxic T lymphocytes from peripheral blood of cancer patients

Accumulation of wild-type or mutant p53 protein occurs in similar to 50% of human malignancies. This overexpression may generate antigenic epitopes re cognized by CTLs, Because normal cells have undetectable levels of p53, the se CTLs are likely to be tumor specific. Here, for the first time, we test the hypothesis that full-length wild-type p53 protein can be used for gener ation of an immune response against tumor cells with p53 overexpression, T cells obtained from nine HLA-AZ-positive cancer patients and three HLA-A2-p ositive healthy individuals were stimulated twice with dendritic cells (DCs ) transduced with an adenovirus wild-type p53 (Ad-p53) construct. Significa nt cytotoxicity was detected against HLA-AZ-positive tumor cells with accum ulation of mutant or wild-type p53 but not against HLA-AZ-positive tumor ce lls with normal (undetectable) levels of p53 or against HLA-AZ-negative tum or cells. This response was specific and mediated by CD8(+) CTLs, These CTL s recognized HLA-A2-positive tumor cells expressing normal levels of p53 pr otein after their transduction with Ad-p53 but not with control adenovirus, Stimulation of T cells with Ad-p53-transduced DCs resulted in generation o f CTLs specific for p53-derived peptide. These data demonstrate that DCs tr ansduced with the wild-type p53 gene were able to induce a specific antitum or immune response, This offers a new promising approach to immunotherapy o f cancer.