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Our immune systems can efficiently identify and destroy abnormal cells. For many years, scientists have debated whether this immune surveillance can efficiently pickup cancer cells and destroy them spontaneously. It is encouraging that white blood cells from a naturally mutated mouse are found to kill aggressive cancer cells. Normal mice injected with the white blood cells from the mutated mice acquired systemic resistance to protect them from developing cancers. Whether this phenomenon in mice can be found in humans needs further investigation. Markedly, we found in our laboratory that a partially purified protein fraction could activate human blood to specifically kill breast cancer cells in vitro. Our study demonstrated that this cancer-specific killing acts through the Complement system, an ancient immune surveillance system to destroy infected and other abnormal cells. We thus hypothesize that human complement is also capable of acquiring the specificity to kill breast cancer cells; however, it lacks a factor that specifically initiates the killing process. In this proposal, we plan to identify 1) the activation factor and 2) the targeted molecules on the surface of human breast cancer cells. Methodologies will involve development of novel affinity chromatographs and application of mass spectrometry-based proteomic approaches. These aims are straightforward and feasible based on our preliminary studies. Accomplishing these experiments will allow us to confirm their function of the activation factor and characterize the mechanism of how these proteins specifically activate our innate immunity to fight breast cancer. Results of the proposed study will become the basis that may lead to development of new strategies for drug discovery. It may explain, at least in part, why some people never get cancer.

Boston University Medical Campus | Boston VA Research Institute 670 Albany St. Pathology 404 | 150 S. Huntington Ave. 1A-320 Boston, MA 02118 | Boston, MA 02130 Tel: (617) 414-7075 | Tel: (857) 364-5611 Fax: (857)364-5627 | Fax: (857)364-5627 jyang@bu.edu | Jinghua.yang@va.gov