A new film to be broadcast on the BBC this weekend looks at the work of scientists at UCL and clinicians at UCLH working together on groundbreaking ‘first in-human’ immunotherapy trials.
These clinical trials are testing new treatments which ‘re-programme’ the immune system to recognise and kill cancer cells, providing a more efficient and less toxic way of treating cancer. At the CR UK & UCL Cancer Trials Centre, both the
CARD and
ALLCAR19 studies are at the forefront of this research.
Between them, UCLH and UCL are leading the largest portfolio of CAR T cell studies in Europe with underpinning support from the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC) and funding by several partners including the blood cancer charity Bloodwise, and the EU 7th Framework Programme.
Dr Martin Pule (UCL Cancer Institute), who leads the UCL CAR T-cell programme and whose work is the main focus of the BBC film 'War in the Blood', said: “CAR T-cell therapy can result in long lasting remissions in patients with blood cancers which have failed all standard treatments. CAR T-cell therapy is a revolutionary new approach in treating cancer.”
Treatments which use the immune system to fight cancer are different to conventional treatments. Our immune system can be much more selective in discriminating between normal and cancerous cells which means that many of the common side-effects of conventional therapies are avoided. Also, immune responses can last for many years, preventing relapse.
Most of the BRC-supported immunotherapy clinical trials focus on using an immune cell called a T-cell to attack cancer. This cell can be imagined as a miniature robot which moves around our bodies, looking for infected cells and killing them. However, T-cells do not recognise most cancers, since cancers develop from our own tissues and appear normal to most T-cells. The main challenge with T-cell immunotherapy approaches is to find ways to direct T-cells to attack cancer cells.
CAR T-cell therapy directs T-cells to attack cancer cells by harvesting T-cells from blood and genetically engineering them outside the body so they are reprogrammed to kill cancer cells. Once they are infused back to the patient, these CAR T-cells act as miniature robot, and find and destroy cancer cells.
BRC director Professor Bryan Williams said the centre had supported the team from outset. He said: “We supported this work because we could see the potential for it to generate new and potentially life-saving treatments for cancer. It is truly remarkable to see the speed at which this has happened - it is an example of research in action in the NHS at its very best.”
For the scientists and clinicians working to develop this treatment, the responsibility of designing and testing new treatments in patients is both exciting and daunting. At the heart of this film is the complex relationship between scientists developing these treatments, the clinical team testing them and the patients receiving the experimental therapies.
UCLH consultant haematologist Dr Claire Roddie (also UCL Cancer Institute) said: “CAR T-cell therapy is a form of personalised treatment for patients who do not respond to standard anti-cancer treatments like chemotherapy and has been shown in trials to cure some patients with cancer, even those with advanced cancers. Most treatments used in patients with end-stage cancer extend life by a few months. For a good proportion of patients, CAR T-cells are resulting in cures. This is unprecedented.”
CAR T-cell therapy has so far shown most promise for haematological (blood) cancers, and Professor Emma Morris (UCL Division of Infection & Immunity) says the therapy represents “a real step change in how we treat cancers. It represents a leap in medical therapies, from using small chemical molecules or proteins to using cells. The complexity of cells means that they can be engineered in highly ingenious ways, leading to treatments with specificity and activity unimaginable in conventional treatments.”
UCLH will open the Sir Naim Dangoor Centre for Cellular Immunotherapy in 2020. This will be an eight-bed unit at UCLH within a new surgery and cancer building made possible by a gift of £1.6 million from the Exilarch’s Foundation, and will build on the world-renowned expertise and groundbreaking advances being made at UCLH to successfully treat cancer using cellular immunotherapy.
At UCLH, Professor Karl Peggs established the clinical translational side of the academic CAR T-cell programme and is now working on setting up Europe’s first dedicated cellular immunotherapy research and treatment centre.
The establishment of this centre will enable UCLH to focus research on advancing cellular immunotherapies. As Prof Peggs says: “While clinical translation of cellular immunotherapy research into blood cancers has already shown positive outcomes, more research is desperately needed. We anticipate that through this research, treatment for other types of cancer – such as skin, ovarian, liver and lung cancers – will be developed, meaning greater cancer survival rates. It is a very exciting development that could be a game changer for the treatment of cancer.”
War in the Blood, produced by Minnow Films for BBC Two, and directed by Arthur Cary, will air on Sunday 7 July at 9pm.
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(Image: Dr Martin Pule and Dr Claire Roddie of UCL’s CAR T-cell programme)