
<ArticleTitle>Specific killing of <prot>P53</prot> mutated tumor cell lines by a cross-reactive human <prot>HLA-A2</prot>-restricted <prot>P53</prot>-specific CTL line.</ArticleTitle>
<AbstractText><prot>p53</prot> is upregulated in the majority of spontaneous tumors and the HLA class I molecule <prot>HLA-A2</prot> is expressed by approximately 50% of the caucasians. Potentially, these facts make <prot>HLA-A2</prot>-binding <prot>p53</prot> peptides for CTL-inducing immunotherapy applicable to a broad range of cancer patients. In our study, we investigated the CTL-inducing capacity of autologous monocyte-derived dendritic cells (DC) maturated by exposure to <prot>CD40L</prot> and pulsed with a pool of 4 wild-type, <prot>HLA-A2</prot>-binding <prot>p53</prot> peptides, and the <prot>p53</prot>-specific <prot>CD8</prot>(+) CTL lines established from healthy <prot>HLA-A2</prot>-positive donors were characterized. Reactivity to <prot>p53</prot>(65-73) and <prot>p53</prot>(187-197) peptides was obtained in the T-cell lines. Interestingly, cold target inhibition experiments demonstrated that the simultaneous recognition of the 2 peptides was the result of cross-reactivity, which was confirmed by killing experiments at the clonal CTL level. Furthermore, 4 <prot>HLA-A2</prot>(+) <prot>p53</prot>-mutated tumor cell lines were lysed by the CTL line, indicating that these peptides are endogenously processed and presented on <prot>HLA-A2</prot> molecule. Thus, monocyte-derived DC pulsed with a pool of peptides are able to induce CTL reactivity to wild-type <prot>p53</prot> peptides presented by several cancer cell lines. In addition, the recognition of 2 different <prot>p53</prot> peptides by the same CTL clone suggests a promiscuous peptide recognition by the TCR involved. Taken together, these in vitro results suggest that vaccination with autologous DC pulsed with multiple <prot>p53</prot> epitopes may induce an effective tumor-specific CTL response in vivo with the potential to eradicate <prot>p53</prot>-upregulated spontaneously occurring tumors.</AbstractText>
