It is a sobering fact that despite decades of research and billions of dollars of funding, cancer death rates have changed little over the past 50 years. What’s more, cancer remissions are often transient, drug resistance is a major problem and drug withdrawal can result in an aggressive return of the disease.
Cancer Immunotherapy was named the breakthrough of the year by the Editorial Board of the highly respected journal Science in December 2013. In immunotherapy, it’s not the disease but the immune system that is targeted. This marks a new therapeutic principle in medical care and is a focus of much of our cancer research at the Malaghan Institute.
When a treatment developed at the Malaghan Institute is tested in patients, it is assessed through a formal clinical trial process by our clinical colleagues in a hospital setting. The trial is managed by a committee of experienced clinical researchers from throughout New Zealand. Data on the safety and efficacy of the new treatment is monitored by another independent group of experts, called a Data Monitoring Committee, who ensure that the information is collected in an unbiassed manner. Only when the study is complete will researchers have access to all of the data to interpret the results. This interpretation is then subjected to further review by international experts before it can be made public, usually in the form of a scientific publication. None of the clinicians and researchers involved can comment publicly until this process has been completed. That way we can be sure the findings are true to our scientific principles.
The immune system has all the properties that are required to complement existing treatments and eradicate cancer. White blood cells called T cells can discriminate between normal and cancer cells, they have powerful cancer killing capability, and can move around the body to eliminate tumours that have spread to other tissues. What’s more, immune cells retain a ‘memory for cancer – so can re-launch an attack should the tumour start to grow again.
An early 20th century surgeon, Dr William Coley, is often credited with first recognising the potential of the immune system for treating cancer. He showed that he could control the growth of some tumours by injecting his patients with killed bacterial infusions (Coley’s Toxins) to stimulate an immune response. Although this was a rather crude approach to cancer treatment, the basic premise of cancer immunotherapy remains the same – to support the immune system in recognising cancer cells, and strengthen its response so that it can destroy them.
We now know that the immune system can be programmed to target cancer cells more precisely through the use of specific vaccines. Cancer vaccines can be created from a patient’s own tumour cells, or from synthetic components made to look like a tumour. The aim is to make the tumour appear dangerous to the body in the same way that an infectious bacterium or virus would, leading to a strong immune response.
The Malaghan Institute is at the forefront of this research with an established international track record going back nearly two decades. We are continually improving our own vaccine technology through basic research in the laboratory, and have conducted clinical trials of different forms of the vaccine in cancer patients.
Leading this work is Associate Professor Ian Hermans, the Malaghan Institute’s Deputy Director of Research. His team is about to undertake a clinical trial of a newly developed melanoma vaccine, in collaboration with Capital & Coast District Health Board, Callaghan Innovation, The University of Auckland and Cancer Trials New Zealand. One of the novel features of this vaccine is the inclusion of the synthetic glycolipid alpha-galactosylceramide (alpha-GalCer), which Associate Professor Hermans’ basic research has shown induces significantly stronger anti-tumour immune responses than vaccines without it.
Complementing our clinical cancer work is an extensive basic research programme involving several of the Institute’s research groups. Professor Franca Ronchese leads a team of immunologists focused on understanding the role of dendritic cells in driving anti-tumour immune responses. Professor Mike Berridge’s research group is exploring how best to combine targeted drug therapies with immunotherapy, with particular emphasis on the new mutant BRAF melanoma drugs. Dr Bridget Stocker’s Immunoglycomics team, now based at Victoria University of Wellington, are developing tailor-made immune ‘modulators’ to switch off unwanted tumour-promoting immune cells. Professor Berridge and Dr Melanie McConnell, now a Senior Lecturer in Genetics at Victoria University, are also utilising their expertise in cell and molecular biology, to investigate the different survival mechanisms used by these cells to withstand current cancer treatments.
By combining the disciplines of immunology, cell biology and drug discovery in translational research programmes that involve immunologists, biochemists, molecular biologists, chemists and clinicians, we believe our research has the potential to launch a new era in cancer treatment.
Cancer Society of New Zealand (National Body and Wellington Division), Foundation for Research, Science & Technology, Genesis Oncology Trust, Health Research Council of New Zealand, Just Paterson Real Estate, Keith Seagar Research Fund, New Zealand Lottery Grants Board - Health Research, The estates of Ellen, Sinclair, Barbara and Alison Wallace, The Royal Society of New Zealand Marsden Fund, The Thompson Family Foundation, Inc. through the Victoria University of Wellington Foundation, Wellington Medical Research Foundation