Acute Myeloid Leukemia, Courtesy of SA Pathology
18 July 2014
Exciting new cancer research, using data collected from the Australian Synchrotron, could lead to a new approach to the treatment of Acute Myeloid Leukaemia (AML). AML is an aggressive form of cancer affecting the blood and bone marrow, and has poor survival rates. Patients can be treated with chemotherapy to induce remission, but there is a high likelihood of relapse.
Published today in major international journal Cell Reports, the research defines precisely how a newly developed therapeutic antibody, CSL362, binds to AML cancer cells. Once bound the antibody is able to recruit the body’s own immune system to kill the cancer cells, potentially preventing relapse of the disease.
The research is a collaborative effort by SA’s Centre for Cancer Biology (CCB), St Vincent’s Institute of Medical Research in Melbourne and global biopharmaceutical company CSL Limited.
CCB Co-Director Professor Angel Lopez says the research showcases the potential of targeted therapy where harm to normal cells and tissues is minimised.
“This research shows how targeted therapy can help the immune system kill AML cells which may extend the lives of patients and cause fewer side effects than other types of cancer treatment,” Prof Lopez says.
“With clinical trials of CSL362 now underway, the article highlights the importance of fundamental research and the benefits of close collaboration between cancer researchers and the pharmaceutical industry.”
The Cell Reports article, ‘Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody’, focuses on the 3-dimensional structure of CSL362 bound to the interleukin-3 (IL-3) receptor. AML cells, in contrast to most normal cells, express high levels of the IL-3 receptor and this provides an opportunity to target and specifically kill the cancer cells.
Article co-author, Dr Tim Hercus from the CCB’s Cytokine Receptor Laboratory, says the research establishes a detailed understanding of how CSL362 binds to the IL-3 receptor and may provide a foundation for the development of next generation therapies targeting the IL-3 receptor and other related receptors.
“Research undertaken at the CCB is directed towards understanding the function of IL-3 and the IL-3 receptor both in healthy individuals as well as in disease settings,” Dr Hercus says.
“Over-expression of the IL-3 receptor in AML is associated with reduced patient survival but at the same time it provides a target to specifically kill the cancer cells.”
Determination of the 3-dimensional atomic structure of CSL362 bound to the IL-3 receptor was the outcome of a long-term collaboration between researchers from CCB, CSL and St Vincent’s Institute of Medical Research.
Dr Sophie Broughton, a co-author and Leukaemia Foundation funded researcher from St Vincent’s Institute, says the structure was determined from data collected at the Australian Synchrotron, a giant x-ray microscope located in Melbourne.
“This structure provides us with a detailed snapshot that reveals how CSL362 interacts with the IL-3 receptor at an atomic level,” Dr Broughton says.
Prof Lopez says while cancer remains a very significant global health issue, there are exciting times ahead.
“It is an exciting time as we move away from conventional methods to more targeted, personalised medicine … one that leads to fewer side effects and more effective treatments,” he says.
“At the CCB we are passionate about innovation in cancer research, and the need to make discoveries that plant the seeds for breakthroughs in cancer. We are proud of this latest research and look forward to continuing work with our partners as it moves through clinical trials.”