The COVID-19 pandemic has brought renewed focus to the great health inequalities between different communities in our society. Looking at cancer care, these inequalities exist across the whole cancer pathway from uptake in screening, likelihood to present early with symptoms, participation in clinical trials, diagnosis and access to treatments. Cancer is one of the leading causes of death globally with 1 in 2 people in the UK being diagnosed in their lifetime, and 28% of people in Greater Manchester dying from the disease each year. In the UK alone, there are around 20,000 extra cancer cases in the most deprived areas. So, what is being done to examine this issue, and what can we do to tackle it?

A combination of causes

Differences across the cancer continuum are born from a combination of structural inequalities, socioeconomic circumstances, socioenvironmental behaviours and lifestyle choices. Gender, racial and educational inequalities also play a part. These complex factors often influence generations and can result in deep-rooted fear and mistrust within communities, leading to barriers to accessing healthcare.

Predominantly, deprivation and lifestyle choices seem to be the most significant contributors, with Cancer Research UK estimating that lifestyle choices cause 40% of our cancers. Greater Manchester is significantly affected by health inequalities. It is the 38th most deprived Sustainability and Transformation Partnership (STP) area in England (of 42), and as a measure of lifestyle choices, it has the 39th highest smoking rate, which is 2% above the England average. These factors go some way to explaining the higher cancer incidences and mortality rates experienced in Greater Manchester compared to other, more affluent areas of the country.

People from the most disadvantaged socioeconomic backgrounds are less likely to attend cancer screening tests and thus likely to present later with their disease. We know that late stage at presentation is a bad prognostic marker: national data show that 49% of the most deprived quintile have early stage at diagnosis versus 58% for the least deprived. The stage can have a huge impact: for example in colorectal cancer, of the four stages, stage one patients have a greater than 90% chance of surviving five years after diagnosis as opposed to stage four patients where the figure is less than 10%.

Additionally, the under-representation of these groups within clinical trials limits the evidence available for better understanding their disease. This means there is a relative lack of understanding of cancer drivers in many marginalised groups, and this limits our ability to tackle it.

In its starkest terms, those who are most disadvantaged in life to begin with, are also most likely to be disproportionately and unfairly affected by a cancer diagnosis, detection and treatment.

From tradition to inclusion

Such disparities need addressing in ways which move from standard, traditional care packages into more inclusive, personalised and diverse packages that benefit those most in need. The pandemic, in revealing the extent of these disparities in healthcare, has proven that it is now essential that they are addressed to achieve significant and lasting change. The health disparities across the cancer continuum can be addressed by interventions such as community screening, community engagement and home-based testing.

Pioneering the move from healthcare models that deliver traditional care and detection packages to those that are more inclusive, diverse and community-focused are essential in helping to redress these deep-rooted health inequalities.

The Lung Health Check pilot

Lung cancer is a deadly disease with a five-year survival rate of only 16% after diagnosis. As lung cancer is most prevalent in areas of deprivation and is a driver of health inequality, it’s a priority for action. In short, lung cancer is by far the biggest cause of cancer death, and those deaths are concentrated in deprived communities.

The ‘Lung Health Check’ (LHC) was an initiative trialled by the lung cancer team at Wythenshawe Hospital (Manchester University NHS Foundation Trust), in partnership with Macmillan Cancer Support. The project took mobile screening units and placed them in public spaces across Manchester that were easy to spot and access for anyone without transport. They advertised their activity as a ‘lung health check’ to dispel fears around cancer and the perceived ‘death sentence’ of a potential lung cancer diagnosis. The locations offered an opportunity to engage with health professionals in a much more informal setting compared to a traditional clinic.

The benefits of the LHC approach were soon clear. It delivered a high number of early detection diagnoses (79% diagnosed at stage one vs a national average of 19.5%) and it engaged with those communities most at risk of this particular cancer. The project showed it could improve patient outcomes and reduce the burden of advanced disease and palliative care costs for the NHS.

The pilot showed a threefold increase in detection of lung cancer at its earlier stages where the tumour is 90% curable and the project has now been rolled out on a local and national scale through the National Targeted Lung Health Check programme, funded by NHS England.

A holistic approach

By taking a holistic approach, other diseases can also be detected at the same time such as Chronic Obstructive Pulmonary Disease (COPD) which is far more common than lung cancer with higher death rates, along with cardiovascular disease. Using the opportunity presented by the Lung Health Check initiative to screen for these three leading causes of premature death will engage hard-to-reach communities and reduce costs to the NHS and patients of late diagnosis. Increased participation of individuals from disadvantaged groups will also have the benefit of increasing their representation within clinical studies and help inform future treatments.

To fully engage with communities, it is vital to reach out to them, make connections and build trust to bring them closer to primary care providers and researchers. It is also essential to capture lived experiences. Multiple initiatives have demonstrated this approach successfully, leading to various forums, patient and public engagement groups and long-term collaborative partnerships. The objective is to build long-lasting and sustainable relationships with communities that levels-up healthcare provision and basic research. By achieving this, individuals will feel their voice can be heard and some of the long-standing issues facing certain communities can be tackled.

Professor Emma Crosbie, Division of Cancer Sciences at Manchester is also working to develop techniques of at-home screening that can help to address cancer inequalities, specifically in female cancers. Lower screening rates found within marginalised groups are posing a problem in gynaecological cancers. An example is work to develop at-home urine tests for Human Papillomavirus (HPV), a precursor for cervical cancer, which it is hoped could address barriers to screening and contribute to improved health equity.

Reaching all communities

Engagement with those communities most at risk of health inequalities such as late cancer diagnosis is vital if a shift to early detection and improved patient outcomes in all communities is to be realised.

Leaders and policymakers within our healthcare service need to put urgent thought into how our system can be structured towards earlier interventions. Increased and meaningful community engagement is key to achieving equitable healthcare and has the added benefits of reduced strain on the NHS from the impacts of late diagnosis. A robust and well-resourced infrastructure is needed to support this.

Barriers and the opportunity for change

There are numerous challenges that come with moving to a diverse healthcare package that engages with disadvantaged and marginalised communities. Implementing successful large-scale community screening involves overcoming problems with the logistics of being based in public spaces, capacity issues, technology barriers and workforce limitations.

Looking at imaging as a diagnostic test for cancer, the UK currently has fewer radiologists per head of population compared with the European average. 2015 figures showed an estimated 4.8 consultant radiologists per 100,000 people. This is one of the lowest figures in Europe, comparing to a mean of 12 radiologists per 100,000 population for Western Europe. These limited numbers of Thoracic Radiology Specialists means reporting on such targeted lung cancer screening scans is problematic in the long term. Similarly, the UK has a significant shortage of CT scanners versus other Organisation for Economic Co-operation and Development (OECD) countries, with latest 2020 To fully engage with communities, it is vital to reach out to them, make connections and build trust to bring them closer to primary care providers and researchers. Leaders and policymakers within our healthcare service need to put urgent thought into how our system can be structured towards earlier interventions. 8 9 data showing the UK has 9.0 CT scanners per million population versus 35 in Germany, 42 in the US, and 70 in Australia.

Restructuring our healthcare system towards prevention and an early detection approach requires reversing the diagnostic and treatment pathway as well as additional funding for services that support early detection. This will also require policy-makers to tackle perceived cultural barriers to encourage screening uptake and engagement with primary care providers.

The Department for Health and Social Care and NHS England have the opportunity to develop innovative cancer services that can reach and engage with all communities. A move towards inclusion is essential not only for those communities who are currently suffering from poor healthcare and the effects of late diagnosis, but also for our healthcare system which isn’t sufficiently resourced to take on the increasing burden of palliative care and treatments which result from these inequalities.

We now need robust and clear leadership on the development of a services, infrastructure and workforce development plan that will support this already world leading detection methodology.

The solutions lie in supporting communities to make healthier choices, making access to healthcare convenient, and reducing unwarranted variation in healthcare through tactical interventions.

Dr Philip Crosbie is a Senior Lecturer in the Division of Infection, Immunity and Respiratory Medicine at The University of Manchester and an Honorary Consultant in Respiratory Medicine based at Wythenshawe Hospital, Manchester University NHS Foundation Trust. His research and clinical focus is the early detection of lung cancer

Dr Suzanne Johnson is a lecturer in the Division of Cancer Sciences and Division lead for Social Responsibility with particular interests in developing inclusive practice in research and teaching and addressing health inequities.  Her background is in basic and translational cancer research, and in 2020 Suzanne was appointed Programme Director to develop a new online Masters programme in Transformative Oncology with The University of Manchester Worldwide.

Professor David Shackley is the Clinical Lead at MAHSC (Manchester Academic Health Science Centre) for cancer working with colleagues to bring research and clinical care closer together. He is the Director of the Greater Manchester Cancer Alliance, and a Consultant Urological Surgeon. From 2015 to 2018 he was the Medical co-lead for the National Cancer Vanguard which brought GM and London together as a 10 million catchment population to develop and test new cancer approaches before a broader roll out across NHS England.

Advanced radiotherapies are redefining the kinds of cancer treatment that are possible. These developments are exciting, but they also present new challenges. One challenge for researchers and clinicians is how to support policy-makers, tasked with developing treatment and care standards across the NHS. So, what are these new treatments, what do they mean for patient choice and what steps can we take to make the most of these opportunities?

Proton Beam Therapy

The Proton Beam Therapy (PBT) Centre at The Christie in Manchester was the first NHS site in the UK to provide radiotherapy using high energy protons to the public. The Centre houses a state-of-the-art particle accelerator that accelerates protons to two-thirds of the speed of light, before delivering them to the tumour site. This precision means that protons can be used in very complex radiotherapy treatments for example treating tumours that are dangerously close to critical organs. Proton therapy is also used for treating children as it causes less damage to healthy tissues and so reduces the chances of ‘secondary malignancies’ (cancers which may have been caused by previous cancer treatments) later in life.

There is a national ‘Indications List’ of the types of tumours proton therapy can best be used on. Referrals are made by clinicians and approved by a national panel with discretion to approve treatments for non-listed tumours, if the tumour location or patient’s anatomy mean that protons are likely to be the most effective method. This provides a valuable flexibility in determining the best course of action for every patient.

FLASH radiotherapy

Another new type of advanced radiotherapy, known as FLASH radiotherapy, is also showing promising signs of becoming a new precision treatment for cancers. At The Christie researchers are using FLASH proton beams in the research room in the clinical PBT centre. FLASH uses very high dose rates and appears to spare normal tissue while still destroying the tumour. Researchers, including teams at The Christie, are undertaking research to understand the mechanisms that cause the FLASH effect. This will also help to understand how FLASH might best be used in the clinic and which patients might benefit most.

MR-LINAC: Integrating imaging directly into treatment

Here at The Christie in Manchester, we have also been developing the use of a new radiotherapy technology known as MR-LINAC. This technology combines Magnetic Resonance (MR) imaging with a photon Linear Accelerator (LINAC), and performs MRI scans during treatment. We are now investigating the potential of this innovation to help clinicians tailor treatment choices based upon an enhanced understanding of the individual patient’s response. MR-LINAC technology offers us the potential for realtime monitoring of the tumour and normal organs during a treatment course, and the agility to adapt that treatment based on what we see. This integration of sophisticated imaging technology directly into the radiotherapy treatment pathway is another breakthrough for Manchester’s cancer sciences research that will enable a new level of personalised, precision treatment.

MR-LINAC treatment is more expensive than standard treatment as it takes longer to deliver and requires more expert input from healthcare professionals (a one hour appointment slot versus a twenty minute appointment), so the gains must be balanced by the increased cost in resources.

These techniques are so early in their development that we are still conducting the research that will allow us to decide the best ways in which this technology can be used in the health service. This evidence will also allow researchers and policy-makers to produce a full costbenefit analysis of material costs, changed outcomes, and overall viability of MR-LINAC treatment as part of the treatment standard for different forms of cancer.

New advances and patient consent and choice

Another new development that we are working on relates to informed consent and the involvement of patients in determining their treatment. Advances in clinical research and technology have allowed us to start work on forms of ‘patient-guided’ radiotherapy, particularly in cases of head and neck cancers. These techniques allow clinicians to present patients with a toolkit that will allow them to understand and play an active role in choosing how their treatments are designed. For example, we will be able to ask patients whether they would rather choose a course of therapy that may impair their hearing against another which might impact their ability to comfortably swallow. Of course, choices like these will not be happy ones, but by bringing the patient in as a fuller participant in their own treatment, we get their full and informed consent for their treatment course. This approach also offers the patient the agency and dignity involved in taking some control over the direction of their treatment.

Ideas and implications

In the field of FLASH radiotherapy, the Cancer Research UK ‘Radiation Research Network’ (RadNet) is currently bringing together clinicians, clinical scientists, radiographers and researchers to discuss which tumours might benefit most from FLASH and start develop of a potential ‘indications list’ for FLASH therapies. The development of this at a national scale (modelled after the existing arrangements for PBT), will be the next step if FLASH radiotherapy delivers on its promises. We see a role for policy-makers in the Department for Health and Social Care, and for parliamentarians with interests in cancer and radiotherapy, to help accelerate the process of getting from clinical discussion into policy and practice.

As researchers, we also seek engagement with and leadership from health policy-makers on the new opportunities for enhanced and informed patient consent. For example, should the use of toolkits such as the one we are developing for head and neck treatments become the norm for bringing patients into decision-making around their own treatments? We are beginning to see how technologies such as the MR-LINAC can play a role in supporting patient choice. A better understanding of treatment response means greater capacity to advise and empower patients to help determine their course of treatment.

While these technologies continue to develop, the discussion about their potential use should be led by the Department for Health and Social Care. It should also involve the National Institute for Health and Care Excellence (NICE), NHS England, NHSX, and the Medicines and Healthcare products Regulatory Agency (MHRA), as well as clinical experts from across the world. This dialogue will benefit from integration into policy discussions via a work programme that we can help to develop between these agencies and the clinical research community.

Building connections, creating new standards

Building and maintaining the connection between advanced radiotherapy research and policy-makers is essential and often overlooked. We as researchers need to show what PBT can achieve and how it can best fit into the treatment landscape. However, we need to understand more about how non-clinical constraints affect public policy and have a regular and ongoing correspondence with decisionmakers to give them a better idea of where our research can help achieve their objectives and, importantly, where it can’t.

In making these recommendations – for supporting the development of a FLASH indications list and national panel formation; for developing a formal work programme to discuss new standards for informed consent in treatment pathways; and for maintaining a sustainable and dynamic forum for correspondence between researchers and policymakers – we seek to show policy audiences the next steps that we need to take.

These clear, measurable, and reachable goals will have far-reaching benefits, moving us closer to the cancer health outcomes made possible by these advanced new technologies.

Karen Kirkby is Professor of Proton Therapy Physics - a joint post between The University of Manchester and The Christie. Karen is responsible for developing a programme of international leading proton research and innovation to deliver direct patient benefits. This goes from basic research, through pre-clinical and translational research to clinical trials.

Professor Ananya Choudhury is Chair and Honorary Consultant in Clinical Oncology at The Christie and The University of Manchester. Ananya specialises in urology and has a strong interest in translational research. She is clinical lead for advanced radiotherapy including the MR-LINAC project and is co-Group Leader of The Translational Radiobiology Group within the Division of Cancer Sciences.

To provide the best care and support for cancer patients during and after treatment, it is essential to collect and work with data that captures patient experiences and patient-reported outcomes. But data is not a simple subject. The way healthcare services work with data, and how we work with patients to collect it, must be tackled from several angles. So, what can be done and what are the priorities?

Challenges with real-world data

To obtain real-world evidence, for example to establish the outcomes of a particular course of treatment and the lessons we can learn for future treatments, it is essential that researchers can easily access high quality real-world data collected (for example from patient electronic health records) and also patient generated health data. Data should be collected in a structured way both at the start of a patient’s journey (diagnosis) and during their treatment pathway. This will allow the capture of demographic, cancer-specific and survival data that could be comparable to the data collected through clinical trials, particularly if quality control processes are built in. At present, the quality of routinely collected data in healthcare settings is still substandard when compared to that gathered in clinical trials, where strict and rigorous processes provide quality assurance.

One of the challenges faced by researchers is the lack of data collected on the impact of a medical condition, such as cancer, and its treatment from the patient's perspective. Clinician-reported data has been found to frequently under-report the frequency and severity of symptoms experienced by patients with cancer. A possible solution is to collect patient-reported outcome measures (PROMs) which are self-completed questionnaires on symptoms and quality of life.

Another challenge is the governance associated with real-world health data. Data sharing is more complex since the introduction of the General Data Protection Regulation (GDPR). To overcome this barrier, an umbrella exemption (Section 251 approval), can be applied for, which first requires NHS ethical approval and a sponsor, and then further applications before permission is granted. Obtaining these umbrella approvals via Section 251 to undertake research with large, real-world datasets is challenging and maintaining public trust regarding data sharing and security is paramount.

Finally, while a positive data culture exists, it is currently hampered by a lack of time and training for most clinical teams who will be involved with the collection of the data.

ePROMS: New ways to capture and use data

The routine collection of electronic patient-reported outcome measures (ePROMS) helps to significantly improve the understanding of the side-effects from treatment and the quality of life for all patients.

The Christie Hospital in Manchester has set up ePROMS as a clinical tool to help improve the communication between patients and clinical teams. The aim is to better tailor treatments and aftercare as well as providing high-quality data to facilitate real-world research. This initiative, a collaboration between The Christie, The University of Manchester and Manchester Cancer Research Centre (MCRC), will also help to enhance many other aspects of routine patient care.

Despite the impact of COVID-19 the roll-out of ePROMS to date has been highly successful, and with funding from The Christie Charity, ePROMS will be rolled out to all relevant disease groups at The Christie by the end of 2022. In addition, a real-time responsive service for patients will be developed in response to patients’ reported symptoms. In this way, ePROMS will feed into models to predict clinical outcomes which may help clinicians to make decisions about treatments. ePROM data may also allow clinic appointments to be used more effectively for patients who require clinical input and reduce unnecessary visits for well patients who do not. Patient care pathways are already becoming personalised as a result of ePROM data. For example, patients receiving Herceptin and other anti-HER2 drugs following surgery for breast cancer are monitored with serial echocardiograms and ePROM questionnaires. Patients who report via ePROM that they are well with no symptoms are able to proceed with treatment without clinical review and patients reporting symptoms via ePROM receive clinical review.

Another recent development in improving the accessibility is our UK Computer Aided Theragnostics (ukCAT) project, launched at Manchester Cancer Research Centre and The Christie in 2017. This system makes anonymised routine patient data available to research organisations who can use those insights to develop new approaches to diagnoses and treatments.

Public consultation and how data is shared

Processes for sharing data in a way that are quick, transparent and acceptable to patients and the public is vital to the ambition to progress towards real-world evidence at scale. The University of Manchester has been working alongside national bodies, including the National Institute for Health Research (NIHR), NHSX, and NDG (National Data Guardian) to run public consultations on the advantages and risks of data sharing.

A recent public consultation, focused on health data sharing in the pandemic, used three citizens’ juries to weigh the benefits of valuable data systems against disadvantages of continuing to process data. Jury members were informed about what data sharing and electronic health records are, why they are important and what the data is used for. This way of bringing complex evidence to the public enabled juries to make judgements and reach reasoned answers to questions concerning data.

The consultation revealed that overall, juries supported decisions to introduce data initiatives during the pandemic and the majority were in favour of all data sharing initiatives continuing, as long as they were valuable. In addition, 94% of jurors believed that an independent body of experts should review data sharing initiatives, rather than those organisations responsible for the initiatives.

Additionally, MCRC’s Patient and Research Data Statement exemplifies the commitment to an ambition of using patient data in a safe and secure way to look at new innovative ways to improve patient outcomes. This has been accomplished through best practice related to patients in research programmes with strict security measures that protect patient confidentiality. Data collected includes real-world data combined with the Greater Manchester Care Record to improve individual cancer care, including diagnosis, treatment and monitoring of cancer. Our system uploads the symptoms, quality of life and experience of patients directly to central and secure data storage at The Christie. This can then be used by both clinicians and patients for them to jointly make informed clinical decisions.

Patient data and steps for the future

There are very few places that have been able to establish ePROMS, or similar patient data initiatives, within a routine setting. Such initiatives require high levels of expertise, engagement with patients and staff, validation of work and in-depth data analysis. To make them a successful and integral part of our own health and care system, we need to take a number of preliminary steps:

• Patient data must be properly linked between primary and secondary care. This results faster communication between both parties and ensures that all relevant information is available in both settings. Leadership from Department for Health and Social Care, NHS England and from our newly developing Integrated Care Systems is key to building this ability.
• To help develop a robust research culture, both current and future clinicians will need further training to understand the importance and clinical relevance of high quality data collection. Organisations like NHSX and Health Education England can play a leading role in setting these standards and delivering the necessary workforce and student training. This should involve a review of current provision of both data collection and quality assurance training, in addition to consultation with researchers and clinicians to develop new content appropriate to our rapidly advancing technologies.
• The process for obtaining permission for the use of data in clinical research must be made easier: opportunities are currently being lost because of the time and complexity required to access the data that researchers need to develop new techniques and treatments, and to co-ordinate healthcare more effectively between organisations within the NHS. We need to explore whether there is space here for exemptions from GDPR and for other regulations to be centrally administered, rather than on a piecemeal basis (where each NHS Trust provides individual exemptions for its data). This must, of course, be accompanied by safeguards and oversight of the highest standards, to ensure public confidence, but these safeguarding standards are already being developed in universities and NHS Trusts across the country and will not be a case of reinventing the wheel.
• We should also listen to our citizens’ juries, who have suggested the formation of an independent body of experts to oversee health data sharing within the NHS and with the research community. This would require a collective initiative, led by central government, to build and establish, but would be supported not only by research organisations around the country but by informed public opinion, as evidenced by our juries’ conclusions.
• It is also essential that data collected from electronic health records can be linked with other digital sources. This requires pragmatic adaptations to GDPR and other data protection laws and working with citizens’ juries to understand the public’s response to new forms of data sharing in the health and social care system.

As we look to the future, building and maintaining public confidence in the integrity and effectiveness in the use of patient data must be understood as the first and essential condition for their future development. Without this, we cannot fully benefit from the promise of real-world evidence research and the great advances in research and treatment that they hold.

Corinne Faivre-Finn is Professor of Thoracic Radiation Oncology, The University of Manchester and Honorary Consultant Clinical Oncologist at The Christie. Her interests lie in the development of advanced radiotherapy techniques, combined modality treatments for non small-cell and small-cell lung cancer, real world and electronic patients-reported outcomes.

Niels Peek is Professor of Health Informatics in the Division of Informatics, Imaging and Data Science (School of Health Sciences), and lead for Digital Health and Care at the Christabel Pankhurst Institute for Health Technology Research and Innovation. His research focuses on translational data science for risk prediction, personalised and precision medicine, patient safety, and multimorbidity.

Dr James Price is a PhD Clinical Research Fellow at The University of Manchester and Consultant Clinical Oncologist at The Christie, where he specialises in the treatment of patients with cancers of the head and neck. He is the Clinical Lead for ePROMs roll-out at The Christie.

The UK in general, and Manchester in particular, has been at the forefront of research into advanced cell and gene therapies for cancer and other diseases. These therapies have the potential to revolutionise outcomes for a wide range of diseases with high levels of morbidity and mortality where standard treatments have proved ineffective. The Government seeks to ‘level up’ the north, and one key aspect of that is expanding its growing specialism in life sciences. But are we investing where we need to and in the facilities that we need to in order to turn this ambition into a reality?

Complex decisions for policy-makers

In the health policy world, we are used to talking about QALYs (Quality-Adjusted Life Years), as the standard to decide whether a medication or intervention is acceptable. A QALY means extending a patient’s life by one year of good health, and the National Institute of Health and Care Excellence (NICE) class a treatment worth the money, if it can add QALYs for £20,000–30,000 or less.

Cell and gene therapies upset these calculations in that they are very expensive, but they do offer a potential cure for some cancers. For patients, whose average prognosis was around five more months of life, advanced cell therapies have led to full remission and recovery. As research into these therapies continues to develop, policy-makers will be faced with increasingly complex decisions about how to compare treatments that extend life (via a number of QALYs) and those that could extend life further or even cure a cancer, but at greater immediate expense.

One way that these costs can be reduced is by shortening supply chains and bringing crucial elements of the production processes that underpin these therapies closer to the research and treatment centres that need them. There have been promising investments made in the north by the Department for Business, Energy and Industrial Strategy (BEIS) and the Medical Research Council to advance this agenda. These include the creation of new ‘bioproduction’ and research facilities in Barnsley (cell production), Sheffield (virus production) and the north-east (Darlington – not a production facility but engaged in optimisation work on existing products).

Bioproduction: The role of manufacturing

The way that some advanced cell therapies, such as ‘CAR-T’ and ‘TIL’ immunotherapies, work is that cells are taken from a patient’s body, we replicate those cells (in a bioproduction facility) and they may then be genetically modified using a virus. This virus enables the cell to produce modified proteins that can help the cell to detect and destroy cancer cells or to treat rare genetic diseases. This requires two different manufacturing processes. We need to be able to make the virus, and also to produce the human cells that the virus is inserted into.

There is a distinct lack of this manufacturing capacity in the north of England. We have one facility planned in Sheffield for virus production, and a cell production facility in Barnsley but nowhere nearby for the insertion of the virus into cells, which is its own distinct and specialised process.

Leading the world: 1% of the population, 12% of the trials

Here in Manchester, the Advanced Therapy Treatment Centre (known as iMATCH) has been working to scale up activity in both cell and gene therapy since 2018. Our work at the centre includes looking at the training needs for staff, challenges in setting up advanced cell therapy trials, and how we can translate research insights into treatments for patients. The Advanced Immunotherapy and Cell Therapy team at The Christie currently has twelve open trials, which is the largest number of solid tumour cell therapy trials taking place in a single centre in the UK.

Despite being leaders in pioneering these treatments, in Manchester and across the UK, we face the considerable expense and logistical challenge of having to purchase and often import the cells we need to work with from other countries. With less than one per cent of the world’s population, the UK is currently conducting 12% of global gene therapy trials. This is a distinctive and valuable edge for the UK’s life sciences sector, but one where we are at significant risk of falling behind unless more investment in domestic bioproduction facilities follows.

‘Levelling up’ through life sciences investment?

With the Government’s commitment to ‘levelling up’ the UK’s regions, and the prioritisation of the life sciences sector as part of its wider Industrial Strategy, now is the time to push for investment in new bioproduction facilities in the north of England. We welcome the investment that led to the virus production facility in Sheffield, but viruses are only one of the two necessary elements for advanced cell therapies. Cell therapy requires both virus production and production capacity for the cells that deliver the virus into the body, making a cell production facility in the north the logical next step to build on that investment.

There are a number of reasons that Greater Manchester in particular stands out as a strong candidate for the location of such a facility:

• A large population of students with experience in biomedical disciplines. This is a valuable skills base that can form a natural talent pipeline for the specialist jobs that a bioproduction plant would create;
• Greater Manchester is well placed for transport, with established links to London and across the Northern Powerhouse region via the ‘M62 Corridor’;
• The University of Manchester is home to the central hub of the national Royce Institute for Advanced Materials. Materials being produced by the Royce, such as hollow-fibre materials for advanced filtration, are already bringing down market prices for the advanced materials needed for this work, and their proximity will allow for greater collaboration and development of new materials in future;
• Manchester is an advanced therapy training centre with several MSc and PhD level programmes in the biotechnology sector, including iMATCH, and already offers specialised hands-on training for the specialised workforce required.

Regardless of its exact location, a cell production facility in the north would create highly skilled jobs, enhance our national research capacity, shorten existing supply chains, and add to the existing life sciences industrial specialisation across Cheshire, Greater Manchester and beyond.

The freedom to set our own regulatory environment for life sciences research in the UK since Brexit is a key strand of government thinking on the future of this sector in the UK economy. To attract more international investment in drug development and human trials, we need to build our own cell production infrastructure, rather than relying on importing the materials we need from the US and other countries.

The US provides one potential model for the UK government to follow. In California, the California Stem Cell Initiative at UCLA was pump-primed with significant federal investment. What followed was the organic development of a life sciences industry cluster, with pharmaceutical companies and research organisations opening laboratories and offices close by. With the Government commitment and industry partnerships underpinned by the post-Brexit Life Sciences Sector Deal, the UCLA example could be replicated here in northern England.

The Office for Life Sciences (a government body ran jointly between BEIS and the Department for Health and Social Care) is best placed to catalyse government engagement with the strategic economic and health benefits that a new bioproduction facility will deliver. We encourage the Office for Life Sciences to convene a working group with representatives from government, industry, research and clinical practice to examine the California/UCLA precedent and its potential application to a new bioproduction facility in the north-west.

With leadership from both national and cityregional government, the next expansion of the northwest’s significant life sciences sector will underwrite new breakthroughs in advanced research, new treatments for many deadly cancers, new high-skill/high-wage jobs, and secure UK leadership in international life sciences investment and exports. The benefits are simply too great for this decision to be delayed or postponed any longer.

Fiona Thistlethwaite is a Medical Oncology Consultant within the Experimental Cancer Medicine Team (ECMT), Advanced Immunotherapy and Cell Therapy (AICT) Team Clinical Lead, Honorary Professor at The University of Manchester, and Director of iMATCH (Innovate Manchester Advanced Therapy Centre Hub). She has an active clinical trials research portfolio in early phase clinical trials (adult solid tumours) within the ECMT and AICT

Brian Bigger is Professor of Cell and Gene Therapy in the Division of Cell Matrix Biology and Regenerative Medicine at The University of Manchester. His Stem Cell and Neurotherapies lab works on the development and delivery of clinical cell and gene therapies for rare genetic diseases and brain tumours. He is also Chairman of the European Study Group on Lysosomal Diseases (ESGLD).

With special thanks to our contributors:

Dr Philip Crosbie is a Senior Lecturer in the Division of Infection, Immunity and Respiratory Medicine at The University of Manchester and an Honorary Consultant in Respiratory Medicine based at Wythenshawe Hospital, Manchester University NHS Foundation Trust. His research and clinical focus is the early detection of lung cancer.

Dr Suzanne Johnson is a lecturer in the Division of Cancer Sciences and Division lead for Social Responsibility with particular interests in developing inclusive practice in research and teaching and addressing health inequities.  Her background is in basic and translational cancer research, and in 2020 Suzanne was appointed Programme Director to develop a new online Masters programme in Transformative Oncology with The University of Manchester Worldwide.

Professor David Shackley is the Clinical Lead at MAHSC (Manchester Academic Health Science Centre) for cancer working with colleagues to bring research and clinical care closer together. He is the Director of the Greater Manchester Cancer Alliance, and a Consultant Urological Surgeon. From 2015 to 2018 he was the Medical co-lead for the National Cancer Vanguard which brought GM and London together as a 10 million catchment population to develop and test new cancer approaches before a broader roll out across NHS England.

Dr Dónal Landers is Director of the digital Experimental Cancer Medicine Team, Cancer Research UK Manchester Institute. He is a Clinician and a Fellow of the Faculty of Pharmaceutical Medicine with over 25 years of experience and achievement in early clinical development, clinical practice, healthcare and pharma consulting, and delivering digital health innovation and solutions.

Karen Kirkby is Professor of Proton Therapy Physics - a joint post between The University of Manchester and The Christie. Karen is responsible for developing a programme of international leading proton research and innovation to deliver direct patient benefits. This goes from basic research, through pre-clinical and translational research to clinical trials.

Professor Ananya Choudhury is Chair and Honorary Consultant in Clinical Oncology at The Christie and The University of Manchester. Ananya specialises in urology and has a strong interest in translational research. She is clinical lead for advanced radiotherapy including the MR-LINAC project and is co-Group Leader of The Translational Radiobiology Group within the Division of Cancer Sciences.

Dr Gareth Price is a Senior Lecturer in the Division of Cancer Sciences at The University of Manchester and a clinical scientist at The Christie. His research focuses on the use of data collected during routine care to derive clinical insight, identify potential improvements in treatment, and provide evidence of the impact of innovations and changes to practice on patients’ clinical outcomes.

Corinne Faivre-Finn is Professor of Thoracic Radiation Oncology, The University of Manchester and Honorary Consultant Clinical Oncologist at The Christie. Her interests lie in the development of advanced radiotherapy techniques, combined modality treatments for non small-cell and small cell lung cancer, real word and electronic patients-reported outcomes.

Niels Peek is Professor of Health Informatics in the Division of Informatics, Imaging and Data Science (School of Health Sciences), and lead for Digital Health and Care at the Christabel Pankhurst Institute for Health Technology Research and Innovation. His research focuses on translational data science for risk prediction, personalised and precision medicine, patient safety, and multimorbidity.

Dr James Price is a PhD Clinical Research Fellow at The University of Manchester and Consultant Clinical Oncologist at The Christie, where he specialises in the treatment of patients with cancers of the head and neck. He is the Clinical Lead for ePROMs roll-out at The Christie.

Professor Emma Crosbie is an NIHR Advanced Fellow, Professor and Honorary Consultant Gynaecological Oncologist at The University of Manchester and Manchester University NHS Foundation Trust. She is Cancer Early Detection Lead of the NIHR Manchester Biomedical Research Centre and her research focuses on screening, prevention and early detection of gynaecological cancers.

Fiona Thistlethwaite is a Medical Oncology Consultant within the Experimental Cancer Medicine Team (ECMT), Advanced Immunotherapy and Cell Therapy (AICT) Team Clinical Lead, Honorary Professor at The University of Manchester, and Director of iMATCH (Innovate Manchester Advanced Therapy Centre Hub). She has an active clinical trials research portfolio in early phase clinical trials (adult solid tumours) within the ECMT and AICT.

Brian Bigger is Professor of Cell and Gene Therapy in the Division of Cell Matrix Biology and Regenerative Medicine at The University of Manchester. His Stem Cell and Neurotherapies lab works on the development and delivery of clinical cell and gene therapies for rare genetic diseases and brain tumours. He is also Chairman of the European Study Group on Lysosomal Diseases (ESGLD).

Keith Brennan is the Associate Dean for Internationalisation in the Faculty of Biology, Medicine & Health and Professor of Developmental Signalling in the Division of Cancer Sciences at The University of Manchester. He is particularly interested in how developmental signalling pathway, which control cellular behaviours like proliferation, apoptosis, adhesion and fate, are disrupted during tumour initiation and breast cancer progression.

Dr F. George Njoroge is a member of Board of Directors and Chairman of Scientific Research and Innovation Committee at Kenya Medical Research Institute (KEMRI). He was a former Chief Scientific Adviser at Kenyatta University Teaching, Referral & Research Hospital (KUTRRH). Previously, a Senior Research Fellow at Eli Lilly and Company and a former Director in the Department of Medicinal Chemistry at Merck Research Laboratories. George is an avid drug hunter with a wealth of drug discovery in infectious and cancer therapeutic areas.

Robert Bristow is Director of the Manchester Cancer Research Centre, Professor of Cancer Studies in the Division of Cancer Sciences (The University of Manchester) and Chief Academic Officer at The Christie. His Translational Oncogenomics laboratory within the CRUK Manchester Institute focuses on the role of the tumour microenvironment on therapeutic resistance and metastases and the genetic basis for aggression in both sporadic and hereditary prostate cancers.

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