Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia, with over 4,000 cases in the UK every year. At the moment CLL is incurable, but in recent years, new drugs called B-cell receptor (BCR) inhibitors, have revolutionised treatment.
However, it is not entirely clear how they work and why they are so effective. In addition, some patients can become resistant to these types of drugs.
A new study, led by Professor Mark Cragg at the University of Southampton and funded by The Kay Kendall Leukaemia Fund and Bloodwise, has characterised the molecular mechanisms responsible for how one of these drugs (idelalisib) work.
Published in the journal Leukemia, the study treated blood cells from CLL patients in the laboratory with idelalisib and found it disrupts important survival signals from within the tumour and prevents communication from surrounding cells that help the tumour survive; causing the tumour cells to die.
The response to idelalisib was linked to an increased production of a protein called Bim, which is responsible for the tumour cell death. Their results also showed idelalisib-like drugs can be successfully combined with antibody treatments to more effectively eradicate the cancer and give longer lasting protection, a process called immunochemotherapy. This combination effect is also dependent on Bimk, the researchers found.
Professor Cragg said: “These results are very interesting and positive. We now know how the drug is able to attack and slow the growth of the tumours, but not get rid of it completely. We also know that Bim is required for the death and for the combination effects with antibody treatments. With this knowledge we can design better, more effective combination treatments. In the future, we could even be looking at combinations that will give us a cure for some blood cancers where we don’t currently have that possibility.”
It is this detailed research to better understand new drugs and combinations with immunotherapy that will be taking place in the University of Southampton’s new Centre for Cancer Immunology, which is due to open in 2017.
The centre, which is being built on the Southampton General Hospital, will be the first of its kind in the UK to focus on immunotherapy, a revolutionary new treatment that supercharges the body’s natural defences to find and destroy cancer. The Centre will bring together world-leading specialists and aim is to accelerate research progress and conduct more clinical trials.
Dr Alasdair Rankin, Director of Research at Bloodwise, said: “Idelalisib and other BCR inhibitors have transformed the outlook for patients with CLL, but we are still not entirely clear how they work and why they are so effective. We now have a rising number of treatments available to people with CLL. A deeper understanding of how these drugs work is needed to guide treatment decisions and identify combinations that deliver the best benefits for patients.”