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 form of the epidermal growth factor receptor, is found in a large percentage of breast tumors and thus may be a viable target for immunotherapy. We are developing a bispecific antibody against both EGFRvIII and a T-cell activation antigen to redirect the cytotoxic response of T-cells with a broad range of specificities against breast cancer cells that express EGFRvIII. Prevention and treatment of breast cancer is also advanced via an improved understanding of breast cancer biology. We have developed immunological reagents against the inherited breast cancer susceptibility gene product, BRCA2, and have shown that this protein is expressed at high levels in thymic epithelium, skin, and squamous carcinoma, suggesting a potential role in differentiation. Elucidation of the role this protein plays in normal breast biology may help us to understand why tumorigenesis occurs in hereditary cases, and these findings may also be applicable to non-inherited breast cancer.