For today’s International Clinical Trials Day we are showcasing some of our exciting and cutting edge research.

Immune therapies are now making an increasing impact on cancer treatment. Dr John Maher is a clinical immunologist at the Comprehensive Cancer Centre, King’s College London. His cutting edge research focuses on the development of cellular immunotherapies for patients with refractory solid tumours. This involves genetic programming of patient white blood cells so that they make a new protein called a CAR (main image). His current clinical trial is testing CAR- T cell immunotherapy, produced in-house using the infrastructure of our NIHR Biomedical Research Centre, in patients with otherwise untreatable head and neck cancer.

Dr. John Maher, Clinical Immunologist

Dr. John Maher, Clinical Immunologist

What is your research about?

T-cells are white blood cells that protect us from infection. We can genetically modify these cells using a harmless virus to produce a new protein called a CAR. As a result, these genetically re-programmed T-cells can now recognise and attack the tumour. Currently, CAR T-cell immunotherapy works best in patients with blood cancers. However, our focus is on developing CAR T cells to target solid tumours, which account for more than 90% of all cancers.

We make a lot of new CARs in our laboratory at Guy’s Hospital, which is known as the CAR mechanics lab! CAR-T cell immunotherapy is currently a very trendy area in clinical research, but it is not so widely appreciated that people have been making CAR-T cells for over 30 years. In the NHS there are two approved CAR- T cell drugs for the treatment of blood cancers, while six products are available in various countries in the world.

Why is your research important?

To put our research into perspective, we expect that cancer will have caused the death of more people in the UK over the past 12 months than COVID-19. This estimate is based on published numbers of deaths due to COVID-19 coupled with trends in UK mortality attributed to cancer in recent years. Furthermore, there are concerns that cancer deaths may have increased disproportionately over the past year because of the huge disruption caused by COVID-19.

We currently have a CAR-T cell immunotherapy clinical trial involving patients with head and neck cancer which runs in the NIHR Clinical Research Facility at Guy’s Hospital. The patients we treat are not suitable for any conventional form of treatment such as chemotherapy, surgery or radiotherapy, so our experimental therapy is a last resort for them. We’ve treated 16 patients so far and fortunately we have not seen any severe side effects in any case. Many of the patients also achieved stabilisation of their disease, which provides encouragement

What is your clinical trial about?

Manufacturing facility clean room

Manufacturing facility clean room

Our trial is the first CAR-T cell immunotherapy study in patients with head and neck tumours. We make the CAR-T cells from a blood sample provided by the patient. Working in the NIHR Clinical Research Facility at Guy’s Hospital, we turn that blood sample into a CAR-T cell drug over 2 weeks. At that time, the patient returns to the hospital and receives an injection of CAR-T cells directly into the tumour. The work involves a huge team of doctors, nurses and scientific staff of many types, so it is a real team effort.

The way the CAR works is to enable the modified T cells to identify proteins called ErbB receptors that are found at high levels on the cancer cell. We made this CAR-Tat Guy’s Hospital a number of years ago and, in 2015, we commenced this clinical trial. The first three patients received a low dose and, once we established that this was safe, we treated the next three patients with a higher dose and so on. By this means, we set out to identify the maximum dose that we can safely administer.

What do you predict from your research?

In undertaking this trial, we needed to take baby steps as safety is the first consideration. We have taken the policy of slowly increasing the dose as described above. Now that we know this is safe, we are combining the CAR-T cells with other drugs in order to try to make the treatment more effective.

Would you like to add anything else?

Get in touch at john.maher@kcl.ac.uk if you’re interested in finding out more.

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