Induction of Immunity to a Breast Cancer Associated Mucin in Transgenic Mice Expressing the Human Antigen - A Preclinical Study

摘要

The high incidence of breast cancer in women and the severity of the disease have stimulated a need for improved and novel forms of therapy. MUC1 has been identified as a breast cancer antigen in breast cancer patients. Transgenic mice were prepared that expressed human MUC1. The mice are naturally tolerant to the molecule providing an opportunity to investigate immunotherapeutic strategies in experimental animals that might eventually be applied to breast cancer in patients. A mouse breast cancer cell line was modified to express human MUC1. If was further modified to secrete various immune augmenting cytokines. Immunization of the transgenic mice with cells modified to secrete IL-12 resulted in the generation of robust, cell mediated immunity toward breast cancer. The immunity was long-term. These data point toward an analogous form of treatment of breast cancer in women. In parallel, we tested a novel vaccine prepared by transfer of DNA from mouse breast cancer cells into a highly immunogenic cell line. The transferred DNA was integrated, and expressed. The DNA-based vaccine was found to be effective in the treatment of breast cancer. This form of vaccine has a number of important advantages over other types of vaccines used in the treatment of malignant disease.