Use of Anti-CD47 Antibodies for the Treatment of Cancer

High expression of CD47, a cell surface receptor on several types of cancer cells, has been identified as a ‘don’t eat me signal’ that inhibits their killing by macrophages or NK cells. Conversely, the CD47 antibody B6H12 that blocks SIRPα binding enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance can be independent of SIRPα signaling.

Cancer stems cells (CSCs) are tumorigenic cells that are difficult to target with conventional chemotherapies due to their undifferentiated state. Stem cells also play an important role in the pathogenesis of cancer. CSCs have been reported to express elevated CD47 levels, but the role of CD47 in directly regulating cancer stem cell function has not been examined. 

Researchers at the National Cancer Institute's Laboratory of Pathology found that the absence of CD47 enhances stem cell renewal in vitro and in vivo by increasing expression of four stem cell transcription factors (see related technologies below). More recently, they discovered methods to force differentiation of breast cancer stem cells by targeting the receptor CD47. These methods disrupt EGF receptor signaling and up-regulate tumor suppressor gene expression in breast cancer stem cells from triple negative breast cancers, but have no effect on normal mammary epithelial cells.

Related technologies include:
U. S. Patent 8,236,313; U. S. Patent 8,557,788; U. S. Patent 8,865,672; U. S. Patent No. 8,951,527
U.S. Patent Application No. 61/735,701 filed December 11, 2012
Application PCT/US2014/025989 filed March 13, 2014