Eight Australians are diagnosed with a form of leukaemia every day. While there are treatments, many of these don’t work on all people or produce such serious side effects that the patient has to be withdrawn from treatment.
Researchers at the Monash School of Biomedical Sciences have discovered a marker on leukemic stem cells that should prevent the cancer from spreading. Because the marker is specific for the cancer cells the treatment does not impact healthy cells – meaning that side effects may be limited.
The tumour marker is EphA3, and KB004, an antibody drug that binds to this marker, is undergoing clinical trials at several hospitals in Australia (including the Alfred Hospital) and in the US.
One of the diseases being treated is AML (acute myeloid leukemia), one of the deadliest and hardest to treat of the leukaemias. To date, the outcome of the Phase I trial has been encouraging: as the drug has been well tolerated, even at high doses and has shown encouraging clinical activity. Phase 2 trials are set to begin by the end of this year.
Associate Professor Martin Lackmann from Monash University’s School of Biomedical Sciences has led the team researching the cancer target.
Associate Professor Lackmann and his team have been working on EphA3 for more than 15 years and have found it is present on a wide range of leukemia and lymphoma cells as well as on solid tumours such as brain, lung, colon and prostate cancers. Importantly the marker is almost non-existent on non-tumour cells making it an ideal target for cancer therapy.
Dr Andrew Wei led a clinical team at the Alfred Hospital that has treated some of the 30 patients receiving the anti-cancer agent, which is now called KB004. The trial at the Alfred Hospital is part of a multi-centre open-label Phase 1/2 trial organised and sponsored by KaloBios Pharmaceuticals, a US-based public Biotechnology Company. In the US the clinical trial is being conducted at a number of sites, including the prestigious MD Anderson Cancer Centre in Texas and the Moffitt Cancer Centre in Florida as well as other equally prominent cancer centres.
Realising its potential as a target for anti-cancer therapy, the Lackmann laboratory, together with a team of Australian collaborators including Professors Andrew Boyd from the Queensland Institute of Medical Research, who discovered EphA3, and Andrew Scott from the Ludwig Institute for Cancer Research, developed an early research version of the anti-EphA3 antibody as a potential anti-cancer agent.
“We are very excited to see progression of KB004 into the clinic, and in particular to be part of the multi-centre trial that allows us to treat leukaemia patients at the Alfred Hospital with the new investigational therapy,” Dr Lackmann said when the trial opened in Melbourne earlier this month.
While the current trial is recruiting leukaemia and other hematologic patients, the target protein EphA3 is also present in solid tumours.
“We believe this antibody could provide significant benefit to patients with a broad range of cancer types, given its potential to affect tumour growth through several distinct mechanisms,” Dr Lackmann said.