Using the immune system to treat cancer
There are some really promising new therapies in development, many harnessing the power and longevity of the immune system. Excitingly, two new clinical trials in this area are in blood cancers for which new treatments are desperately needed.
Karl Peggs at UCL will trial a new therapy that involves ‘teaching’ a patient’s own white blood cells to recognise and attack diffuse large B-cell lymphoma cells (DLBCL), a form of non-Hodgkin lymphoma. This could particularly help drug-resistant patients suffering relapse to stay fit enough for a stem cell transplant. Paresh Vyas at Oxford will test a new targeted drug that is designed to lift the ‘invisibility cloak’ acute myeloid leukaemia (AML) cells use to hide from the immune system, so that it can launch a killer attack.
Two other projects, thinking a bit more laterally, aim to exploit the immune system’s infection-fighting ability. Kate Bailey, an up-and-coming research haematologist at UCL, will genetically ‘reprogram’ measles viruses to selectively infect acute lymphoblastic leukaemia (ALL) cells from adults. Mark Cobbold’s PhD student at Birmingham will design a drug that sticks to the surface of myeloma cells and tricks the patient’s immune system into recognising the cancers cells as being infected. In both these cases, the idea is to mark the cancer cells out for an immune attack, and these approaches will be tested first in patient cells and mice to check they can work.
And we’re ensuring we’re investing in the future in this area – in both research and researchers. Zumla Cader, a promising junior scientist at Birmingham, will visit Harvard, USA for two years to study how Hodgkin lymphoma cells evade the immune system by analysing cells from patients. Ali Roghanian, another ambitious junior scientist currently at Southampton, will spend two years at MIT, also in the US, using mice to characterise proteins he's recently identified as doing the same in AML. At Birmingham, Graham Taylor’s new three-year project will support a junior research fellow to interrogate DLBCL patient samples to discover the immune defects that allow the disease to develop and the role the Epstein-Barr virus plays in certain forms of the disease. All these projects hope to ultimately develop similar therapies to Prof Vyas’, whilst also supporting early career researchers to develop independent skills and experience.
Hitting the roots of blood cancers
A group of projects are focusing on drug resistance in chronic lymphocytic leukaemia (CLL), reflecting the fact that there are as yet no cures for this disease. For example, a major five-year research programme in Birmingham, led by Tanja Stankovic, will use human cells and mice to test new ways to selectively kill certain types of drug-resistant CLL cells by exploiting weaknesses in their ability to properly repair DNA.
Two three-year projects at Southampton, run by Andrew Steele and Francesco Forconi, will use cultured and isolated leukaemia cells to find the signals from the tissues surrounding CLL cells that boost their growth and survival, and work out how these sorts of stimuli act differently on CLL cells that have different genetic faults. Another, led by Simon Wagner at Leicester, will study how the activity of certain genes protects CLL cells from the effects of therapy. These projects aim to help researchers design better therapies that target the biological roots of CLL and, crucially, inform doctors about which patients are likely to benefit from which therapies.
Other projects are looking at the molecules and signals that pull the strings in other blood cancers. Over the next three years, Reuben Tooze at Leeds will use cultured lymphoma cells to study a master regulator in a certain form of DLBCL to devise new ways to get at the heart of this cancer. By using isolated human cells, mice and computer modelling to map the entire network of master regulators in chronic myeloid leukaemia, Tessa Holyoake and David Vetrie at Glasgow aim to deliver true cures in this disease. Their teams are focusing on the leukaemia master ‘stem cells’ – the small number of cells that do not generally grow rapidly but which can seed new tumours. They are hard to target with current drugs and may be why the disease is difficult to eradicate completely.
New treatments for rare diseases
Many of the diseases already mentioned are amongst the more common blood cancers, but it’s vital that new treatments for developed for all.
Steve Knapper at Cardiff, for instance, will trial a new targeted drug, tefinostat, for chronic myelomonocytic leukaemia – a disease that affects around 450 people in the UK each year, with over half of patients dying within two years of diagnosis. Kim Orchard at Southampton is hoping to improve treatment for AL amyloidosis, a rare condition that without treatment is usually fatal within a few months from diagnosis. This trial will use a form of targeted radiation to destroy the abnormal cells without damaging normal tissues, which if successful could also be used in patients with myeloma.
Stopping blood cancers in the first place
A couple of projects aim to get to the heart of how blood cancers actually start. Anindita Roy, a research haematologist at Oxford, will use a two-year fellowship to look at the first genetic changes that occur in the founder cells of leukaemias affecting very young babies. Mel Greaves at The Institute of Cancer Research in Sutton will take this one step on by continuing his work to define the 'second hit' genetic errors necessary for childhood ALL to form. By using patient-derived cells and mice to understand the events that take place early in leukaemia development, researchers may be able to find ways to prevent these diseases from starting.
Also, thinking prevention, Jackie Boultwood at Oxford aims to apply a gene editing technique developed only last year to correct genetic faults in myelodysplastic syndromes (MDS) – a group of blood disorders that affect proper blood cell production. To get the technology working, this will initially be done in cultured cells.
Most cases of MDS and AML result from genetic mistakes picked up over a patient's lifetime, but a handful of cases arise because because a person has inherited genetic faults that increase their likelihood of a cancer developing. A major five-year programme at Queen Mary University of London, led by Inderjeet Dokal, Jude Fitzgibbon and Tom Vulliamy, hopes to increase our understanding and improve the management of patients who have these inherited forms of MDS and AML.
All of these projects are driving towards stopping people dying from blood cancers – or even getting them in the first place – as well as improving the lives of patients both during and after treatment. Many thanks to all those all have supported us and continue to do so – this work would not be possible without you.
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