Antibody homes in on leukaemic stem cells

Source: CSL

Preliminary results from a murine study of a novel monoclonal antibody therapy for acute myeloid leukaemia (AML) shows that the antibody seems to reduce the proliferation of leukaemic stem cells (LSCs), which are thought to be a major barrier to conventional treatments.

The resistance of LSCs to chemotherapy is thought to be a big reason the treatment does not work in most patients, leading to attempts to overcome these cells' effects.

The results, presented by Associate Professor Richard Lock, of Sydney's Children's Cancer Institute, are based on work to target leukaemic stem cells, first identified by Professor John Dick at the University of Toronto, one of the key authors of the study.

The antibody used in the research, 7G3, was first created by Dr Angel Lopez of the Hanson Institute at the University of Adelaide.

The antibody homes in on the CD123 receptor on the surface of the stem cell, blocking its function, growth and survival. CD123, or the interleukin-3 receptor alpha chain, is a marker for leukaemic stem cells.

CD123 is also found on the surface of normal blood stem cells but not in great numbers, meaning that the antibody should not affect normal blood cell development.

The research presented at the ASH meeting describes the results of treatment with 7G3 in irradiated immune-deficient mice.

Two central experiments were undertaken in the project. The first involved human AML stem cells, which were treated with 7G3 and then injected into the mice. A control group of mice were injected with untreated AML stem cells.

The overall survival of treated engrafted mice was higher, surviving for 24 weeks as opposed to 11.5 weeks for the control group.

7G3 was also administered to mice with established AML. The injection of 7G3 reduced AML dissemination around the body and the ability of LSCs to re-establish leukaemia as secondary transplants into other animals was reduced.

Exposure to 7G3 had little effect on normal human bone marrow stem cells, the study found.

"These results show that 7G3 is able to target LSCs to prevent them moving around and proliferating in mice, while at the same time having little effect on normal blood cells," Lock said.

"This is a very exciting finding because it is one of the first drugs that have 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 leukaemia without many of the side effects of current drugs."

CSL is funding the project in association with the University Health Network in Toronto; the Institute of Medical and Veterinary Science and the Hanson Institute in South Australia; the Children's Cancer Institute and the Queensland Institute for Medical Research.