Bringing tomorrow’s medicines to patients today

Working together to scale up cancer research activity and develop best practice is what Professor Fiona Thistlethwaite considers is the answer to increasing Manchester’s ability to deliver cell therapy clinical trials. She tells us how links across the city are being strengthened in order to help advance these cutting-edge treatments.

Delivery of clinical trials of advanced cell therapy is always going be complicated but my ambition is to make delivery as routine as other clinical trials and treatments. By organisations working together to develop the systems and infrastructure to do this, more patients in Manchester will have opportunities to participate in these trials and ultimately bring tomorrow’s treatments to patients earlier.

Advanced cell therapy uses the patient’s own cells to fight disease. My particular focus is on the use of a patient’s own T-lymphocyte cells (T-cells) to attack their cancer. These cells can be gene-modified or selected to increase their activity against the cancer, making this a personalised form of immunotherapy.

Trial complexities

These are challenging trials to run because they involve many different steps and processes.

At the clinical site there will be an initial assessment period to see if a patient is suitable for the trial and whether they wish to participate. We then need to acquire the appropriate cells, manipulate them in the laboratory and eventually return the cells to the patient, usually done by infusion, so that they can fight the patient’s cancer. In this context the cells are referred to as advanced therapy medicinal products (ATMPs).

Before we give the cells back, a patient may need chemotherapy as a conditioning treatment and we also need to frequently give other drugs to support the cells. Unfortunately these additional interventions can add to the side effects and often mean that patients have to stay in hospital for a significant length of time.

These multiple steps make developing standardised processes very challenging.

Collection and manufacture of the ATMP is variable, depending largely on which type of cells are required for the treatment. Some cells need to be  collected by a process called leukapheresis,  where the patient is connected to a machine for several hours to extract sufficient lymphocytes from their blood, while others are taken from a piece of the tumour itself so the patients must undergo surgery.

These cells then have to be transported at the correct temperature to the manufacturing laboratory where they are manipulated..

Once they have been genetically modified, the cells need to be expanded to very high numbers under sterile conditions before they can be returned to the patient.

Team working

At the moment these trials involve relatively small numbers of patients, however they still require a high level of coordination across many different teams to ensure the ATMPs are safely delivered to patients.

At the clinical site for every cell therapy trial, in addition to doctors like myself, there are the nursing teams who will administer the cells to the patient when they are ready and look after the patient as an inpatient.

We need to link into laboratory teams, not just where they are manufacturing the cells but where we may be doing some immune monitoring to check the levels of cells in a patient. There are the pathology teams who store the cells and who coordinate release of the cells in collaboration with pharmacists who ensure that the products are safely dispensed.

At The Christie, to ensure the high level of coordination that is required, we have set up a specialist Cell Therapy Team which is focusing on getting more of these trials up and running. This team is working to equip more staff with the skills and knowledge required to manage patients on cell therapy trials.

Upscale activity to improve outputs

Up until now, cell therapy studies have often been run as small, academic investigator-led trials with just a small team working hard to deliver them. To take these trials and therapies to the next level I believe we need to work together to reach a critical mass of activity across Manchester which will make trials more efficient to deliver.

By doing this we can increase the number of patients and look to run larger scale trials in both the investigator-led and commercial setting. It’s here where the unique aspects of Manchester come to the forefront because of our existing clinical centres of excellence, our close geographical co-location, our existing links to commercial partners and our ability to successfully operate in a progressive landscape of innovation.

Meeting future challenges

Although my focus is on using cells to treat cancer, there are many other applications of cell therapy to other diseases such as childhood genetic diseases and degenerative diseases. Working with colleagues at The Christie, The University of Manchester, Manchester University NHS Foundation Trust and nine commercial partners, we have formed a new consortium, iMATCH (Innovate Manchester Advanced Therapy Centre Hub).

We believe that by working together we can scale up our activity in these complex therapies across Manchester in both the adult and paediatric, cancer and non-cancer settings. iMATCH has recently been successful in its bid for almost £7 million in funding over three years from Innovate UK to become one of three national advanced therapy treatment centres.

All three centres will work together to form a UK network which we hope will maximise the potential for cell therapy development in the UK. All too often we see ground-breaking research originate in the UK, but then fail to capitalise on those early advances in terms of taking research beyond small early-phase clinical trials to later phase trials, and ultimately to commercialisation. We hope that by forming this national network to share best practice and optimise collaborative working we can secure the UK as a global hub for cell therapies.

I have been hugely impressed by the ‘can-do’ attitude here that has enabled us to rapidly turn what was just an idea a few months ago into a three year programme of work that I believe reflects the team science approach in Manchester.

Without buy-in from many senior NHS, academic and industry leaders it would simply not have been possible and I doubt there are many places in the UK where it could be done. As a busy NHS consultant it’s very easy to become focused on day to day firefighting and management of patients, and while patients are quite rightly central to everything we do, it is always challenging to think of the bigger picture.

The opportunity is here to form those networks and work together to be able to deliver on the big projects and ultimately bring effective treatments to more patients, more quickly.