CD47 as a target for new cancer treatment

CD47 is a 50 kDa integral membrane protein composed of an extracellular IgV domain, five transmembrane domains and a short C-terminal cytoplasmic tail with four alternatively spliced forms. The protein is expressed on most human cells and the different CD47 forms show tissue specific distribution. CD47 functions as an essential component of the innate immune system by interacting with the signal regulatory protein alpha (SIRPα) expressed on macrophages activating a response that inhibits cell phagocytosis, also known as the “don’t eat me”-signal.

Cancer cells exploit this control mechanism by overexpressing CD47 to evade the immune system and enhance survival. By targeting unique determinants on the IgV CD47 domain we have demonstrated that ligation of CD47 also may induce very fast and efficient programmed cell death in cancer cells. Several studies in vivo demonstrate that blocking of CD47/ SIRPα interactions must be combined with additional cancer drugs to sufficiently eliminate cancer cells.

Our anti CD47, CO-1, reveals unique and promising features as it eliminates cancer cells through a dual approach. It both acts as a checkpoint inhibitor by blocking of CD47/SIRPα interactions, increasing cancer cell phagocytosis, as well as induction of fast and direct CD47-mediated cell death of cancer cells. This bifunctionality of our anti-CD47 monoclonal antibody provides us with the opportunity to develop a new and improved immunotherapy option for cancer patients.

CD47 mAB CO-1 Other CD47 mAb
Immediate direct tumor cell killing (PCD) Yes No
Blockade of CD47/SIRPα Yes Yes
Demonstrated tumor elimination in NSG mice as monotherapy Yes No
High affinity binding to CD47 Yes No
Unique/different epitopes Yes Yes

About Caedo Oncology

Caedo Oncology develops new strategies for monoclonal antibody based therapy based on activation of distinctive pathways for cell death in cancer cells and blocking checkpoint inhibitors.

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