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

摘要

Micrometastasis of breast cancers prior to detection and surgical resection often limits the success of current cancer therapies. New methods to treat and to prevent metastatic breast cancer are thus urgently needed. Treatments based upon immunotherapy have recently gained support, due to the high specificity of immune recognition and the resultant potential for decreased complications related to treatment. This project has focused on development of reagents for passive immunotherapy of breast cancer, based on a variant of the epidermal growth factor receptor (EGFRvIlI) found in over 27% of breast cancers. We have genetically engineered constructs for an antibody bispecific for EGFRvIII and the CD3(epsilon) T cell activation antigen. This bispecific antibody should be capable of redirecting the cytotoxic response of T cells with a broad range of specificities against breast cancer cells that express EGFRvIII. We have also constructed an adenovirus that efficiently transduces the EGFRvIll gene into a variety of target cells to facilitate in vitro testing of the bispecific antibody. These reagents are available to researchers interested in further testing and characterization of this promising passive immunotherapy approach.