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 SIRPα, 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 SIRPα variants with differential ability to bind to human CD47 and showed
that when SIRPα 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 SIRPα-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 SIRPα 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 at www.oicr.on.ca.
University Health Network
University Health Network consists of Toronto General, Toronto Western,
Princess Margaret and Toronto Rehab. The scope of research and
complexity of cases at University Health Network has made it a national
and international source for discovery, education and patient care. It
has the largest hospital-based research program in Canada, with major
research in cardiology, transplantation, neurosciences, oncology,
surgical innovation, infectious diseases, genomic medicine and
rehabilitation medicine. University Health Network is a research
hospital affiliated with the University of Toronto. www.uhn.ca.
The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the
world's foremost paediatric health-care institutions and is Canada's
leading centre dedicated to advancing children's health through the
integration of patient care, research and education. Founded in 1875
and affiliated with the University of Toronto, SickKids is one of
Canada's most research-intensive hospitals and has generated
discoveries that have helped children globally. Its mission is to
provide the best in complex and specialized family-centred care;
pioneer scientific and clinical advancements; share expertise; foster
an academic environment that nurtures health-care professionals; and
champion an accessible, comprehensive and sustainable child health
system. SickKids is proud of its vision for Healthier Children. A
Better World. For more information, please visit www.sickkids.ca.
SOURCE: Ontario Institute for Cancer Research
