Role of the Complement Inhibitor CD59 on Breast Cancer Cells

摘要

It is proposed that reversing the effects of CD59, a tumor cell expressed complement inhibitor, will allow effective immune-mediated clearance of tumor cells and improve prospects for successful immunotherapy. CD59 function is species selective, and we have determined species selectivity of human mouse and CD59, an important consideration for establishing human models of human cancer in rodents for the study of complement. We have expanded our study to include other tumor expressed complement inhibitors and have shown for the first time in vivo that expression of complement inhibitors on a tumor cell has functional consequences with regard to complement deposition and tumor growth. These studies have also established a rodent model of human breast cancer that is relevant for testing complement-associated immune mechanisms and may be relevant for pre-clinically evaluating complement activating anti-tumor antibodies. We have further identified the individual residues that confer human CD59 species selective activity. This data is an important step toward identifying the three dimensional structure of the CD59-C9 peptide ligand complex and may assist in design of CD59 inhibitors.