Current treatment for breast cancer involves surgical resection followed by radiation and/or chemotherapy, and outcomes are highly dependent on the extent of spread of the tumor at the time of diagnosis. New strategies are needed to prevent relapse by eliminating residual tumor cells after primary treatment. Cancer vaccines represent an attractive possibility, as breast tumors are accessible to the immune system and frequently elicit cellular and hormonal immune responses to mutated or overexpressed proteins. Enhancement of helper and cytotoxic T cell responses to breast tumors through vaccination could potentially lead to the thorough and specific elimination of micrometastatic cells. This form of immunotherapy might be most effective for the treatment of early-stage disease, where residual tumor cells are generally fewer in number and, theoretically, of more stable and consistent genotype. It is hypothesized that (1) early-stage breast tumors express a set of proteins yet to be identified that elicit antibody and T cell responses in a significant proportion of patients with early-stage disease, and (2) such proteins, by virtue of their ability to break immunological tolerance, are optimal candidates for target antigens in a therapeutic vaccine. This application describes a strategy to identify novel immunogenic gene products expressed in early stage breast cancer using a serum antibody-based screening method known as SEREX. These gene products will be systematically evaluated as candidate vaccine targets by first determining the pattern of mRNA expression across a panel of primary breast tumor specimens and normal tissues. Those that exhibit frequent and abundant expression will be analyzed for antibody, helper T cell, and cytotoxic T cell responses in breast cancer patients and normal controls to identify a subset that is commonly immunogenic in humans. Two additional candidate antigens, EGFRvIII and IGF-1R, which share features with the well-characterized breast cancer antigen HER2/neu, will also be evaluated by these criteria. Tumor proteins that demonstrate antibody and T cell immunogenicity in a significant proportion of breast cancer patients will be excellent candidates for future vaccine development and, ultimately, clinical studies in women with early-stage breast cancer.
