Study reveals possible method of removing leukemia stem cells, preventing relapse of Acute Myeloid Leukemia

TORONTO, Sept. 3, 2012 /CNW/ - New research published today in the Journal of Experimental Medicine may provide a new avenue for the treatment of Acute Myeloid Leukemia (AML) and a solution to the high rate of disease relapse experienced by patients. The study identified a protein interaction that limits the immune response to AML and provides a method to disrupt it.

The study was led by Drs. Jean Wang, Affiliate Scientist at the Ontario Cancer Institute (OCI), the research arm of the University Health Network's Princess Margaret Hospital, John Dick, leader of the Ontario Institute for Cancer Research's (OICR) Cancer Stem Cells Program and Senior Scientist at the OCI, and Jayne Danska, Senior Scientist, The Hospital for Sick Children (SickKids) Research Institute.

Their study found that a protein on the surface of AML cells called CD47 binds to a protein called SIRP, causing macrophages to develop immune tolerance to AML cells. Macrophages are cells of the immune system capable of phagocytosis, an 'eating' process that removes pathogens, aged and abnormal cells from the body. The researchers generated mice that expressed SIRP variants with differential ability to bind to human CD47 and showed that when SIRP signalling was absent macrophages were able to clear human leukemia stem cells (LSC). This finding is significant, as it is believed that relapse of disease is driven by LSCs that survive conventional chemotherapy.

The researchers then confirmed these results by treating mice that had been engrafted with human AML with a novel protein called SIRP-Fc that can block CD47 on the leukemia cells. They found that treatment with the protein enhanced phagocytosis of AML cells by macrophages and reduced AML growth in the mice. Additionally, treatment with the protein did not cause increased phagocytosis of normal blood stem cells.

The team is working to develop leukemia therapeutics based on the concept of antagonizing SIRP signalling and allowing the patient's own macrophages to remove any LSCs that survive standard therapies.

"This study is an important step forward in our understanding of leukemia stem cells and has opened the door to a new line of therapies that could have a significant clinical impact by preventing relapse of AML. I commend Drs. Wang, Dick and Danska and their colleagues for their outstanding work," says Dr. Tom Hudson, President and Scientific Director of OICR.

"This work provides a new avenue for treating leukemia by remobilizing the body's immune defenses against the leukemia cells. Importantly, this approach could kill the 'roots' of the leukemia with potentially less toxins than traditional anti-leukemia therapies," says Dr. Benjamin Neel, Director and Senior Scientist, OCI.

"This study is an excellent example of translating research into a potential clinical application. This collaboration began several years ago by our discovery that CD47-SIRPa interactions were important to the growth of normal blood and leukemia cells, that translated to the development of a blocking protein that exposes LSC to immune attack," says Danska. "We are optimistic that clinical development of this therapy will contribute to more effective, less toxic treatments for many kinds of leukemia by eliminating LSC."

Ontario Institute for Cancer Research

OICR is an innovative cancer research and development institute dedicated to prevention, early detection, diagnosis and treatment of cancer. The Institute is an independent, not-for-profit corporation, supported by the Government of Ontario. The annual budget for OICR, its research partners and collaborators exceeds $150 million. This supports more than 1,600 investigators, clinician scientists, research staff and trainees located at its headquarters and in research institutes and academia across the Province of Ontario. It has research hubs in Hamilton, Kingston, London, Ottawa, Thunder Bay and Toronto. OICR has key research efforts underway in small molecules, biologics, stem cells, imaging, genomics, informatics and bio-computing, from early stage research to Phase III clinical trials. For more information, please visit the website atwww.oicr.on.ca.

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Study reveals possible method of removing leukemia stem cells, preventing relapse of Acute Myeloid Leukemia