ACCUMULATION OF THE P53 PROTEIN ALLOWS RECOGNITION BY HUMAN CTL OF A WILD-TYPE P53 EPITOPE PRESENTED BY BREAST CARCINOMAS AND MELANOMAS

The p53 protein is accumulated in tumor cells of many human cancers an d can elicit in vivo humoral and proliferative responses. Rare reports about p53-mediated tumor recognition by CTLs have remained questioned . We therefore studied a panel of breast tumor and melanoma cell lines that we assayed for the presence of accumulated p53 and surface HLA-A Z and for the presentation of p53 epitopes. From PBMC of a healthy don or, we have generated a CTL line, D5/L9V, directed against HLA-A2-rest ricted peptide 264-272 from wild-type p53. It efficiently lysed breast adenocarcinomas MCF-7, MCF7/RA1, and MDA-MB-231, and melanoma M8, whi ch all accumulate the p53 protein. Using competition assays, we made s ure that tumor lysis by D5/L9V was due to recognition of endogenously produced p53 peptide 264-272 associated with the HLA-A2.1 molecule on the surface of these tumor cells. Cells with undetectable levels of wi ld-type p53, such as lymphoblastoid cells and melanoma M74, were not r ecognized by D5/L9V. Neither were breast tumor cell line MCF7/ADR nor melanoma line M44 because of HLA loss. This study therefore shows that it is possible to obtain in vitro CTL lines that specifically recogni ze a p53 epitope spontaneously presented by a variety of HLA-A2(+) tra nsformed cell lines provided they display abnormal patterns of p53 exp ression, This work points out that breast tumors and melanomas share a p53 epitope, and raises hopes for future immunotherapeutic approaches .