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
Competitive Advantages:
Monoclonal antibodies that directly target CD47-expressing cancers
Commercial Applications:
- Treatment for breast cancer and other cancers
- Antibodies for biomedical research
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E-086-2012
TAB-4265
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E-153-2008
TAB-4430
Radioprotectants and Tumor Radiosensitizers Targeting Thrombospondin-1 and CD47 -
E-227-2006
TAB-4296
Methods of preventing tissue ischemia -
E-296-2011
TAB-4315
Modulating Chemotherapeutic Cytotoxicity
Patents
- US
Provisional (PRV) 62/062,675
Filed on 2014-10-10
Status: Abandoned - Patent Cooperation Treaty
(PCT) PCT/US2015/055029
Filed on 2015-10-09
Status: Expired - Australia
National Stage 2015329696
Filed on 2015-10-09
Status: Abandoned - Canada
National Stage 2964173
Filed on 2015-10-09
Status: Pending - European Patent
National Stage 15788253.1
Filed on 2015-10-09
Status: Issued - US Patent 11,053,314
Filed on 2017-04-06
Status: Issued - Germany
European patent (EP) 15788253.1
Filed on 2015-10-09
Status: Issued - France
European patent (EP) 15788253.1
Filed on 2015-10-09
Status: Issued - United Kingdom
European patent (EP) 15788253.1
Filed on 2015-10-09
Status: Issued - US
Continuation (CON) 17/346,630
Filed on 2021-06-14
Status: Pending - Australia
Divisional (DIV) 2021204818
Filed on 2021-07-09
Status: Issued
Collaborations
- Licensing
- Collaboration