Immunity to HER-1/neu Protein

摘要

The HER-2/neu (HER2) proto-oncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER2 over-expression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The overall goal for the proposal is to develop the knowledge base necessary to develop vaccine and T cell therapy strategies directed against HER2. Preliminary studies prior to the grant discovered that some patients with breast cancer have existent CD4+ helper T cell immunity and antibody-mediated immunity to HER2. HER2 is a self protein. Therefore, before our studies it had been assumed that patients would be immunologically tolerant to HER2 and that immunity could not be generated. Our prior studies demonstrating that immunity is already present in some patients with breast cancer implied that immunity to HER2 is induced in some individuals by virtue of the presence of growing cancer expressing the antigen and gives credence to the concept that HER2-specific immunity can potentially be used in therapy without destroying normal tissue. The current grant is exploring issues important for developing HER2 specific vaccines and T cell therapy.