| First Author | Cicinnati VR | Year | 2005 |
| Journal | Int J Cancer | Volume | 113 |
| Issue | 6 | Pages | 961-70 |
| PubMed ID | 15514940 | Mgi Jnum | J:95100 |
| Mgi Id | MGI:3525026 | Doi | 10.1002/ijc.20686 |
| Citation | Cicinnati VR, et al. (2005) Impact of p53-based immunization on primary chemically-induced tumors. Int J Cancer 113(6):961-70 |
| abstractText | In mice as well as humans, cytotoxic T lymphocytes (CTL) specific for wild-type-sequence (wt) p53 peptides have been shown to react against a wide range of tumors, but not normal cells. As such, they are attractive candidates for developing broadly applicable cancer vaccines. Of particular interest is the potential of using p53-based vaccines in high-risk individuals to prevent cancer. Methylcholanthrene, an immunosuppressive polycyclic hydrocarbon carcinogen implicated as a causative agent in human cancers, has long been used to induce murine tumors with a high incidence of genetic alterations and sensitivity to wt p53-specific CTL. To analyze the potential of p53-based vaccines on primary tumors, we evaluated the efficacy of DNA and dendritic cell vaccines targeting wt p53 peptides given to methylcholanthrene-treated mice in the protection or therapy settings. The results indicate that the efficacy of these vaccines relative to reducing tumor incidence were severely compromised by vaccine-induced tumor escape. As compared to tumors induced in non-immunized mice, a higher incidence of epitope-loss tumors was detected in tumors from the immunized mice. The increase in tumor escape arose as a consequence of either increased frequencies of mutations within/flanking p53 epitope-coding regions or downregulation of expression of the major histocompatibility complex Class I molecules that present these epitopes for T cell recognition These findings are consistent with current views of immunoselection occurring in patients receiving tumor peptide-based immunotherapy, and impact on the design and implementation of p53-based vaccines, in particular, those aimed at treating individuals at high risk for developing cancer. (c) 2004 Wiley-Liss, Inc. |
