Breast Cancer Vaccines that Overcome Tolerance and Immune Suppression
Abstract
Our previous studies indicated that Ii- vaccines are more efficient in CD4+ T-cell activation than Ii+ cells, and that mouse MHC II vaccines caused regression of established tumors in mice. In vitro studies with human MHC II vaccines demonstrated that the Iivaccines activated a population of CD4+ T-cells that is distinct from the population activated by Ii+ cells. This observation is consistent with our hypothesis that the absence of Ii results in the presentation of novel MHC II peptides. We have now identified peptides of four vaccines: MCF10/DR7/CD80, MCF10/DR7/CD80/Ii, MCF10/CIITA/CD80, and MCF10/CIITA/CD80/Ii siRNA. For every vaccine cell line two affinity purifications were performed, and for every affinity purification two LC-MS/MS runs were conducted. Peptides present in both affinity purifications and with Peptide Prophet probability scores above 0.05 were further analyzed. One hundred sixteen peptides were identified for MCF10/DR7/CD80 and 228 peptides for MCF10/DR7/CD80/Ii; 52 peptides were present in both cell lines (Fig 1A). One hundred eight peptides were identified for MCF10/CIITA/CD80 and 28 peptides for MCF10/CIITA/CD80/Ii siRNA cells, with 6 peptides common to both cell lines (Fig 1B). These findings are consistent with our hypothesis that Ii+ and Ii- MHC II vaccines present distinct peptide repertoires. Seven peptides were chosen to be best binders by Artificial Neural Net MHC II peptide prediction by our bionformatician collaborator Dr. Michael O Neill. All of these seven peptides have been shown to be immunogenic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2012
- Accession Number
- ADA559253
Entities
People
- Olesya Chornoguz
Organizations
- University of Maryland, Baltimore