Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer, Based on Epidermal Growth Factor Receptor Variant, Type III.

摘要

Prevention of metastatic breast cancer is limited to early detection and surgical resection of a localized tumor. Treatment for advanced breast cancer is often unsuccessful due to micrometastasis of the tumor prior to therapy. Thus, new methods to treat and prevent metastatic breast cancer are sorely needed. EGFRvIII, a variant of the epidermal growth factor receptor, is found in a large percentage of breast cancers but not in normal adult tissues and is thus a viable target for immunotherapy. We are studying two approaches to induce a cytotoxic response against EGFRvIII-bearing tumors. The first approach increases the sensitization of cytotoxic T-cells by enhancing loading of antigen onto host antigen presenting cells, making these cells extremely effective at presenting antigen to the immune system. The second approach utilizes a bispecific antibody against both EGFRvIII and a T-cell activation antigen redirecting the cytotoxic response of T-cells with a broad range of specificities against breast cancer cells that express EGFRvIII. These studies will result in an increased understanding of the role of EGFRvIII in breast cancer biology. Additional benefits include the development of specific, non- toxic, and effective immunotherapies for treatment and prevention of breast cancer and other tumor types.