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 Ii- vaccines 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2011
- Accession Number
- ADA542725
Entities
People
- Olesya Chornoguz
Organizations
- University of Maryland, Baltimore