Activation of macrophages via inhibition of CD47 signaling is a novel therapeutic approach to cancers. Phagocytosis depends upon the balance of pro-phagocytic and anti-phagocytic inputs. Cancer cells express various pro-phagocytic signals such as calreticulin and phosphatidyl serine but counter these with increased expression of CD47. Binding of CD47 to its receptor SIRPa on macrophages initiates a signal cascade, resulting in inhibition of phagocytosis. Blocking CD47 from interaction with SIRPa results in phagocytosis of the cancer cells. Irv Weissman’s group at Stanford has developed a humanized monoclonal anti-CD47 antibody Hu5F9-G4 that has remarkable anticancer activity in many human cancers in preclinical studies, including ovarian cancer (OC) xenografts. The underlying hypothesis of this proposal is that activation of macrophages against serous ovarian cancers will provide a novel and effective therapy for this disease. It is a treatment that may have clinical benefit as a single agent, but much more importantly may add to the small but real curative benefit of existing regimens.