Complement Inhibitory Proteins and Their Role in Tumorigenesis

摘要

Complement is a major effector mechanism of the immune system. Membrane complement inhibitors on the surface of breast tumor cells, may play a crucial role in determining tumorigenesis and the outcome of antibody-mediated immunotherapy. The objective of this proposal is to determine the role of complement and complement inhibitors in tumorigenesis and to determine whether reversing the effects of tumor-expressed complement inhibitors will allow effective immune-mediated clearance of tumor cells. We have established rodent models of human cancer that are suitable for evaluating the role of complement and complement inhibitors in the growth and control of breast cancer (and is likely applicable to many types of cancer). We have shown for the first time in vivo that a complement inhibitor expressed on a tumor cell surface can promote tumor growth, and have shown that different complement associated effector mechanisms can operate to control tumor growth.