The effectiveness of the currently available cancer chemotherapy is severely limited due to side effects to healthy tissues. It is widely believed that the targeted delivery of cytotoxic effector molecules to the tumor tissue could greatly improve the anticancer effect. The first step in developing this type of therapy for the treatment of breast cancer is the identification of targeting vehicles, such as monoclonal antibodies which bind specifically to breast tumor tissue. Previous work has identified several antigens expressed on breast tumors but none of these are ideally suited as targets for immunotoxins. If the immunoconjugate therapy is to be effective, it is of absolute importance that the antigen is cell specific, expressed on the surface of the cell and is not shed into the sera. We propose a novel method that will lead to the identification of breast tumor specific cell surface antigens. Subtractive hybridization has been used successfully to identify differentially expressed genes, and we will apply this methodology to create a cDNA library that is highly enriched in sequences that encode breast tumor specific antigens. Expression of this library in a murine cell line will create a novel set of antigens that should upon immunization lead to antibodies with the desired breast tumor restricted specificity.Awardee's statement of the potential commercial applications of the research: Breast cancer has reached epidemic proportions in the United States; an estimated 175,000 new cases will be diagnosed this year. We propose a method to develop immunoconjugate therapy in order to target anticancer therapeutics directly to the tumor cells. These therapies have the potential to be extremely specific as well as potent.National Cancer Institute (NCI)
