Cell therapy based methods to reduce tumor growth by disrupting the CD47-SIRPα interaction and targeting cells for phagocytosis with antibodies.

Current cancer treatments (i.e. radiation, chemotherapy, etc.) result in multiple serious side effects due to lack of treatment specificity.  Cancer immunotherapies in development target the CD47-SIRPα interaction in order to incite local macrophages to engulf cancer cells, but tumor associated macrophages in solid tumors do not exhibit strong anti-tumor properties. In addition, CD47 is abundant on all healthy cells, so that targeting CD47 will generally harm healthy cells and lead to a variety of unwanted side effects such as anemia.  A therapy that enhances macrophage phagocytosis specifically of tumor cells and also avoids broad targeting of CD47 will reduce tumor size without the complications of current treatment regimens.

The Discher Lab has developed a method to selectively enhance phagocytosis of cancer cells by macrophages. More specifically, the researchers have demonstrated efficacious treatment of solid tumors by a mechanism of macrophage infiltration and stimulation combined with CD47-SIRPα disruption. A reduction in tumor size comparable to, or better than, chemotherapeutic treatments was observed in mouse models together with maintenance of normal parameters for blood and body weight. This approach will allow for a treatment strategy in which cancer cells are selectively targeted for phagocytosis via macrophages while healthy cells are unaffected.

• Bone marrow derived macrophages and antibodies readily penetrate solid tumors from circulation
• Injected cells and antibodies did not cause significant anemia, thrombocytopenia, or weight loss in mice
• Phagocytosis of tumor cell subpopulations in both tumor periphery and core
• Cost-effective treatment