P53 Immune Response in Breast Cancer Patients: Assessment of CTL recognizing the HLA-A2.1 Restricted, Wild-Type Sequence p53 264-272 Epitope.

摘要

Approximately 30% of breast cancer patients are p53 sero-positive and have detectable anti-p53 T cell proliferative responses. Tumors expressing mutant p53 molecules have an enhanced potential to present wild- type-sequence (wt) p53 epitopes derived from mutant p53 for T-cell recognition. Vaccines targeting these epitopes would be broadly applicable. HLA-A2.l-restricted CTL- recognizing wt P53 264-272 and 149-157 peptides have been generated from PBMC obtained from healthy donors and/or oral cancer patients. A subset of these donors were found to be non-responsive to the P53 264-272 peptide, and altered peptide ligands of this epitope were identified that induced CTL from PBMC that were non-responsive to the parental peptide. Currently, precursor CTL (pCTL) for the P53 264-272 epitope present in unstimulated PBMC can be identified by 4- color flow cytometry using soluble PE-conjugated HLA-AO2Ol/p53 peptide tetrameric complexes (tetramers). An analysis of anti-p53 pCTL in the peripheral circulation and tumors of breast cancer patients was done with tetramers for the wt P53 264-272 and 149-157 peptides. An analysis of genomic p53 exons 5-8 of the patients' tumors, when available, was also performed. The results of this study provide a basis for further investigation of the anti-p53 responses of breast cancer patients and will facilitate p53-based immunotherapy of breast cancer.