Accession Number:

ADA413081

Title:

P53 Immune Responses in Breast Cancer Patients: Assessment of CTL Recognizing the HLA-A2.1 Restricted, Wild-type Sequence p53 (264-272) Epitope; Frequencies of Tetramer+ T Cells Specific for the Wild-Type Sequence P53 (264-272) Peptide in the Circulation of Patients with Head and Neck Cancer; The Ability of Variant Peptides to Reverse the Nonresponsiveness of T Lymphocytes to the Wild-Type Sequence P53 (264-272) Epitope

Descriptive Note:

Final rept. 1 Oct 2000 - 30 Sep 2002

Corporate Author:

PITTSBURGH UNIV PA SCHOOL OF MEDICINE

Report Date:

2002-10-01

Pagination or Media Count:

37.0

Abstract:

This document contains three papers focusing on the analysis of anti-p53 cellular immune responses of breast, head, neck, and oral cancer patients. The research was undertaken to provide insights into the potential of p53-based vaccines for immunotherapy of these cancers. The first paper, by Albert B. DeLeo, is entitled p53 Immune Responses in Breast Cancer Patients Assessment of CTL Recognizing the HLA-A2.1 Restricted, Wild-type Sequence p53 264-272 Epitope. In this study, methodologies were developed to detect anti-wild-type p53 CD8 and CD4 T-cells present in the peripheral circulation and tumor infiltrating lymphocytes TILs obtained from cancer patients by flow cytometry analysis using soluble HLApeptide tetramers. In the second paper, Frequencies of Tetramer T Cells Specific for the Wild-Type Sequence p53 264-272 Peptide in the Circulation of Patients with Head and Neck Cancer, by Thomas K. Hoffmann, et al. Cancer Research v62 p3521-3529, June 15 2002, frequencies of wild-type p53 264-272 peptide-specific CD8 T cells were determined in the peripheral circulation of patients with squamous cell carcinoma of the head and neck SCCHN. T cells of 30 HLA-A2.1 patients and 31 HLA-A2.1 healthy individuals were evaluated by multicolor flow cytometry analysis using peptide HLA-A2.1 complexes tetramers. The third study, The Ability of Variant Peptides to Reverse the Nonresponsiveness of T Lymphocytes to the Wild-Type Sequence p53 264-272 Epitope, by Thomas K. Hoffmann et al. Journal of Immunology v168 p1338-1347, 2002, sought to increase the responsive rate to the wild-type p53 264-272 peptide of peripheral blood mononuclear cells PBMC obtained from normal donors and patients by identifying more immunogenic variants of this peptide. Two such variants were generated by amino acid exchanges at positions 6 6T and 7 7W of the peptide. The 7W variant peptide has potential for immunotherapy of nonresponsive oral cancer patients.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE