A potential new approach to treating AML

A more detailed understanding of how the therapeutic antibody CSL362 binds to the interleukin-3 (IL-3) receptor may provide a new approach to treating acute myeloid leukaemia (AML).

AML blood films, courtesy SA Pathology.

AML is an aggressive cancer that affects the blood and bone marrow. The cancer develops in the myeloid cells of the bone marrow and is characterised by an overproduction of immature myeloid cells. The disease has poor survival rates. Patients can be treated with chemotherapy to induce remission, but there is a high likelihood of relapse.

The research defines precisely how a newly developed therapeutic antibody, CSL362, binds to the interleukin-3 receptor on AML cancer cells. AML cells, in contrast to most normal cells, express high levels of the IL-3 receptor. Once bound CSL362 recruits the body’s immune system to kill the cancer cells, potentially preventing relapse of the disease.

The long-term collaborative study was conducted by researchers at the Centre for Cancer Biology (CCB) at SA Pathology in Adelaide, St Vincent’s Institute of Medical Research in Melbourne and global biopharmaceutical company CSL.

CCB Co-Director Professor Angel Lopez, who was recently elected a Fellow of the Australian Academy of Science, said the research realises the potential biological therapies have in minimising harm to normal cells and tissues.

“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,” Lopez said in a statement.

The study determined the three-dimensional atomic structure of CSL362 bound to the IL-3 receptor. The crystal structure revealed that the N-terminal domain of the IL-3 receptor adopted unique ‘open’ and classical ‘closed’ conformations.

The researchers note that a more detailed understanding of how CSL362 interacts with the IL-3 receptor at an atomic level provides the framework for the development of next-generation antibodies to target the IL-3 receptor and other related receptors.

Clinical trials of the CSL362 antibody are underway.

The study was published in Cell Reports.