Cancer therapy goal for researcher

Life work culminates in testing of cancer therapy in humans

The Queensland Institute of Medical Research announced today that a potential cancer treatment is being tested in humans for the first time.

Phase I clinical trials have commenced using KB004. Phase I trials are the first step in a systematic process to determine if a drug might be efficacious in humans. The monoclonal antibody has been shown to kill certain types of cancerous tumours in a laboratory using human samples. It is targeted towards EphA3 expressing hematologic malignancies, which are believed to account for about 50% of acute leukaemias as well as a number of other human cancers including a significant proportion of malignant melanomas, brain tumours and lung cancers.

For QIMR researcher Professor Andrew Boyd, the journey from the initial identification of the antibody to the stage of clinical testing has been long but very rewarding. “The KB004 project has a special place in my heart as it originated in my own lab many years ago. Although it now involves two other research groups in Australia and a U.S. company, there is a sense of nearing the goal I set out to achieve when I first started my research career,” said Professor Boyd, Head of QIMR’s Leukaemia Foundation Laboratory.

KaloBios Pharmaceuticals, a South San Francisco biotech company took the original mouse antibody and through a process known as Humaneering(TM) technology, developed an antibody that could be used in humans as it would be more likely to be tolerated by the human immune system.

“The initiation of a Phase I clinical trial in patients with acute leukaemia by KaloBios is an important landmark and will hopefully lead to further testing and the ultimate use of this antibody as a treatment. As Leukaemia Foundation Professor of Experimental Haematology at University of Queensland and a consultant Haematologist at the Royal Brisbane Hospital, it is highly significant to me that the phase I trial is in leukaemia, the disease that drove me to the initial discovery.”

“I was motivated to enter research by the hope that I might do something which improved the lot of all patients with leukaemia and related diseases – this is an immensely gratifying event.”

The antibody works by targeting a receptor protein found thus far in cancer cells and not on normal white blood cells or normal stem cells. It is hoped it will be well tolerated in patients with little or no side effects.

The development of this antibody as anti-cancer therapeutic was a collaboration between QIMR’s Professor Andrew Boyd, Professor Andrew Scott from the Ludwig Institute and Associate Professor Martin Lackmann from Monash University, who initiated and lead the translational aspects of this venture. It would not have been possible without ongoing financial support for Professor Boyd from the Leukaemia Foundation.

KB004 is a first-in-class engineered IgG1κ antibody targeting the EphA3 receptor tyrosine kinase. Developed using KaloBios’ proprietary antibody Humaneering™ technology, KB004 has variable regions that are very similar to human germ-line sequences, providing the potential for low immunogenicity in patients. In addition, KB004 is engineered to enhance antibody-dependent cytotoxic (ADCC) activity.