Studies Show Promise For Novel Antibody Therapy To Treat Acute Myeloid Leukemia
Acute Myeloid Leukemia
CSL Limited has presented data, which demonstrate the promising pre-clinical activity of a novel monoclonal antibody, in the potential treatment of acute myeloid leukemia (AML).
AML is an aggressive cancer of white blood cells and most commonly occurs in adults. It is usually treated with chemotherapy but the cure rate in adults is only about 30%. About 9,000 deaths from AML occur each year in the United States(1). The novel antibody specifically targets the "core cell" of AML, called the leukemic stem cell (LSC) which was first identified in the laboratory of Professor John Dick, one of the key authors of the study(2). It is currently thought that the resistance of leukemic stem cells to chemotherapy is a major reason for the inability to cure most AML, and that improving the outlook for patients with AML will require elimination of these cells.
The antibody used in the research, called 7G3, was first created by Dr Angel Lopez at the Hanson Centre for Cancer Research in Adelaide, South Australia. It hones in on CD123 (IL-3 receptor alpha chain) on the surface of the LSC, blocking its function, growth and survival. CD123 is found on the surface of normal blood stem cells much less frequently, and 7G3 should therefore have no effect on normal blood cell development.
The research presented at the ASH meeting by key investigator Associate Professor Richard Lock of Children's Cancer Institute Australia for Medical Research in Sydney, describes the results of treatment with 7G3 of irradiated immune-deficient mice with AML.
Two central experiments were undertaken; firstly human AML stem cells were treated with 7G3 and then injected into the mice, which were compared with a control group of mice injected with untreated AML stem cells. The overall survival of treated engrafted mice was significantly improved with the median survival of control group 11.5 weeks versus 24 weeks for the antibody-treated group.
Secondly, 7G3 was administered to mice with established AML. Administration of the antibody to these mice reduced AML dissemination around the body of the mice. The ability of leukemic stem cells from mice treated in this way to reestablish leukemia as secondary transplants into other animals was markedly reduced.
In contrast, exposure to 7G3 had little effect on normal human bone marrow stem cells.
"These results show that 7G3 is able to target LSC's to prevent them from moving around and proliferating in the mice, while at the same time having little effect on normal blood cells," said Dr Lock at the ASH meeting today.
"This is a very exciting finding because it is one of the first drugs that has been designed to specifically target the LSC, rather than simply attacking the cancer cells proliferating in the blood and bone marrow. Hopefully this means that it can fight leukemia without many of the side effects of current drugs. It opens up an exciting new option for the treatment of AML," he said.
CSL wishes to acknowledge the contribution of the University Health Network in Toronto, Canada, The Institute of Medical and Veterinary Science/Hanson Institute for Cancer Research in South Australia, Children's Cancer Institute Australia for Medical Research in Sydney, Australia and the Queensland Institute for Medical Research, Australia, its key collaborators in this important project.