The Identification of Breast Tumor Antigens Targeted by the Immune Response during Tumor Rejection
Abstract
Previous studies from our laboratory have shown that breast cancer patients can be successfully immunized with HER-2/neu (HER2) peptide vaccines resulting in epitope spreading and improved survival. In autoimmunity, epitope spreading is associated with tissue destruction and may explain why our patients had improved survival. Identifying those antigens to which epitope spreading occurred in this population of breast cancer patients may prove useful in developing cancer vaccine strategies. Our hypothesis is that these antigens may be tumor rejection antigens. The specific aim of this proposal was to identify potential "tumor rejection" antigens using sera derived from breast cancer patients immunized with a HER2 peptide-based vaccine who demonstrated epitope spreading and prolonged survival after active immunization. To achieve this objective, we used the technique of serological analysis of recombinant cDNA expression libraries (SEREX) to screen for tumor-specific antigens. The work was divided into 3 tasks (1) construction of breast cancer cDNA libraries from 2 breast cancer cell lines, (2) to perform SEREX to identify potential tumor rejection antigens, and (3) to identify the antigens using DNA sequencing. The first aim was achieved by constructing cDNA libraries from 2 lines, SKBR3 and MCF7. We have screened these libraries with patient and normal serum and have recovered several putative candidate antigens. Three has been sequenced and are called Homo sapiens hypothetical protein MGC2574, Sjogren's Syndrome Autoantigen B, and Recombining binding protein suppressor of hairless. These immune response to these proteins are being studied to determine whether they may be ture tumor rejection antigens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA431332
Entities
People
- Keith L Knutson
Organizations
- University of Washington