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Novel imaging device enters first round of development funding programme

Proton-beam-therapy (PBT) is becoming increasingly important for treating cancer, with projected increases of up to 50% more patients per year being treated with the technology in the UK and worldwide by 2025.

Although the precision of PBT has many advantages over traditional radiotherapy, there some uncertainty over the range of delivery the beam provides. There is risk of potential overdose to normal tissues or underdose to tumour, resulting in reduced tumour-control and long-term side-effects due to treatment of healthy tissue. This can be detrimental to patients and a burden on healthcare systems if side-effects become apparent later in a patient’s life.

Therefore, a method to verify the range of treatment beams when using PBT on patients is crucial to increase the treatment accuracy. Dr Anna Vella, Postdoctoral with the Radiation Therapy Medical Physics Group, led by Prof. Frank Van Den Heuvel, at the University of Oxford’s Department of Oncology, is investigating the efficacy of a device with this purpose.

Anna is leading CAPULET (Coded Aperture Prompt-gamma Ultra-Light imaging detector), an imaging device for quality assurance assessment of radiotherapy plan efficacy, designed for daily use in clinical practice. CAPULET could be installed onto a variety of PBT devices, and used to verify and fine-tune the dose between fractions in particle-beam radiotherapy. It does this through collecting 3D images of the particle beam penetrating soft-tissue, with the ultimate goal to fine-tune planning doses and improving the efficacy of the overall radiotherapy treatment.

This novel and unique technology is faster & more compact than current devices, increases the field-of-view, and improves the signal-to-noise ratio. The impact on patients will be to improve cancer-control, fewer complications, and improved quality-of-life following treatment.

CAPULET has recently been selected as one of 35 projects in the Pre-Development Phase of the Alderley Park Oncology Development Programme – a national programme designed to develop and progress start-up oncology projects. Funded by Innovate UK and Cancer Research UK. It will now be work-shopped, and potentially be chosen to join the full development programme with grant funding.

Proof-of-concept experiments will be performed in collaboration with the CRUK-funded ART-NET. The long-term plan of CAPULET is to develop a large-area detector to fully image the beam delivery range within lungs, liver, H&N and other large sites in the human body to overcome limited field-of-view found in other existing devices on the market.

New partnership enables access to state-of-the-art radiotherapy machine

The first NHS patient has received treatment on the cutting-edge ViewRay MRIdian technology, thanks to a new partnership between the University of Oxford, Oxford University Hospitals (OUH) NHS Foundation Trust and GenesisCare.

The partners, with the support of the John Black Charitable Foundation, have collaborated to establish a ten-year programme of clinical treatment for NHS patients, with further research into improving cancer treatment using the Viewray MRIdian.

Due to the natural, unavoidable movement of soft tissue inside the body, normal tissue around the cancer can be exposed to radiotherapy treatment, particularly when targeting soft-tissue tumours deep within the body. It can be challenging to visualise these organs during radiotherapy with routine radiotherapy delivery.

The ViewRay MRIdian machine is the only one of its kind in the UK, with only 41 machines worldwide. It allows doctors to see the normal soft tissue and the tumour in real time by combining MRI scanning with targeted radiotherapy. Incorporating MRI scans will allow doctors to then tailor doses in real time to the specific internal anatomy of the patient on the day of treatment.

MRIdian technology also minimises the damage to surrounding healthy tissues by switching off when tumour tissue moves outside of the targeted beam. This could mean less side effects for patients and increased dosage of treatment delivered directly to the tumour.

GenesisCare, the University of Oxford and OUH will also partner in research collaborations to develop real-world evidence which will inform future utilisation of the MRIdian technology in hard-to-reach tumours, such as pancreatic cancers. The research partnership will assess the benefits of the MRIdian technology in terms of improved cancer outcomes and reduced toxicity.

Elizabeth Rapple, from South Oxfordshire, is the first patient to use the machine to treat her renal cancer, as part of the new partnership. She says:

“I feel very fortunate to be able to access this machine as part of a new Oxford-wide partnership. Any operation to remove my tumour would have been highly invasive, so it’s lucky that my cancer was suitable for MRIdian radiotherapy. I am so grateful that this unique machine has been made accessible through the NHS, and that I can be the first of many to benefit from this partnership going forward.”

Project leader Professor Tim Maughan, from the University of Oxford, said:

“Treating patients on the MRIdian is like a surgeon putting on their spectacles for an operation – for the first time we can see exactly what the cancer is doing during treatment and adapt to change accordingly.  This accuracy allows us to reduce side effects and we hope to improve cancer outcomes in hard-to-treat cancers.”

Dr James Good, Clinical Oncologist at GenesisCare, said:

“The MRIdian machine is at the cutting-edge of what is possible in radiotherapy technology. The ability to visualise the tumour more accurately, to follow it while it’s being treated and to adapt the plan every day means we can deliver the best possible outcomes.

“This collaboration with the University of Oxford and Oxford University Hospitals will be truly beneficial for cancer patients in the UK. Not only will it provide patients who otherwise would have limited, or sadly, no options with a really viable treatment option, but we can also help demonstrate the effectiveness of this treatment, with the ambition to make it available for all NHS patients in the future.”

Carol Scott, Lead Therapeutic Radiographer & Deputy Clinical Director at Oxford University Hospitals , said:

“OUH are excited to be part of this collaboration offering NHS patients the opportunity to take part in these clinical trials. The use of daily advanced imaging that clearly shows us the tumour and normal soft tissue around it will enable us to take the next step in making our treatments even more personalised and effective”

Prof Andi Roy receives new award for immune-cell research

Co-funded by Cancer Research UK and Children with Cancer UK, Andi is one of 5 to receive £1 million each to investigate children’s and young people’s cancers.

Improving immunotherapy through epigenetics

Immunotherapy has shown remarkable efficacy against a range of cancers. One approach, termed immune checkpoint blockade therapy, blocks an inhibitory immune receptor called PD-1 to take the brakes off the immune system and allow it to kill cancer cells. However, despite this success, anti-PD-1 therapy is ineffective in the majority of cancer patients.

Research is underway to discover strategies that can overcome tumour resistance to immunotherapy. A promising avenue for further investigation is the manipulation of epigenetic regulators. Epigenetic regulators influence the expression of genes without changing the underlying DNA sequence. They can dampen the response of the immune system and their inhibition has been shown to enhance the response to anti-PD-1 treatment. However, because epigenetic regulators are involved in several aspects of the anti-tumour immune response, inhibiting them can result in potentially opposing effects, with the result of little or no overall benefit.

In this paper published in the journal Cancer Discovery, Professor Yang Shi and his laboratory explore the opposing effects of inhibiting one such epigenetic regulator, LSD1. Using mouse and tumour cell models, they show that when LSD1 is repressed, there is a greater immune cell infiltration into the tumour but this is counteracted by the increased production of a cell regulatory protein called TGF-β that suppresses the ability of these infiltrating immune cells to kill cancer cells.

To tackle these conflicting effects, the team experimentally depleted both LSD1 and TGF-β during anti-PD-1 therapy and demonstrated a significant increase in immune cell infiltration, cytotoxicity and cancer cell killing. This combination treatment led to eradication of these previously resistant tumours and long-lasting protection from tumour re-challenge, making it a promising future strategy for increasing the efficacy of this important class of cancer treatment.

New Oxford spin-out Singula Bio launches

Singula Bio is a bold new seed-stage biotechnology company spun out of Oxford University. It aims to become a world leader in developing neoantigen-based individualised cell therapies to use against difficult-to-treat solid malignancies such as ovarian cancer.

This patient-centred approach will pioneer immunological, medical, surgical and computational technologies to generate selective therapies that eliminate cancer, and the ultimate hope is to achieve long-term, high-quality disease-free survival for cancer patients.

Singula Bio was co-founded by Professors Ahmed Ahmed, Enzo Cerundolo and Enda McVeigh from the Nuffield Department of Women’s & Reproductive Health at Oxford University. It is supported by Oxford University Innovation (OUI), the University’s research commercialisation company, and it has secured generous seed-stage investment from IIU Nominees Limited to pursue its goals. Singula Bio is a landmark for OUI as it is the 250th OUI-supported venture to have passed through the office since it opened its doors in 1987.

Motivated by their many patients (and laboratory funding from charities Ovarian Cancer Action and Cancer Research UK) Profs Ahmed and Cerundolo were inspired to improve an individual’s gruelling experience of cancer and to lessen their suffering of other treatments. Together, they have an enormous knowledge in cancer medicine, cancer immunology, cell and molecular biology, and computational biology which has enabled them to design patient-specific cancer cell therapies that harness the power of the patient’s own immune system to fight cancer.

In a tumour, cancer cells carry mutations that appear foreign to a patient’s body and, therefore, their immune system reacts to these mutations. One strong form of an immune reaction is through generating mutation-specific cells called “T cells”.

Prof Ahmed, Professor of Gynaecological Oncology at the Nuffield Department of Women’s & Reproductive Health, Oxford University, said:

“A key feature of cancer cells is the preponderance of genetic aberrations in their DNA. These aberrations can make proteins appear foreign to our body’s immune system which then develops immune cells (T cells) to fight cancer cells. Thanks to years of research and technology development we now know how to identify relevant tumour-specific T cells to grow them outside the body and deliver them back to patients to fight cancer cells.”

Understanding how cancer arises from infected tissue

Whilst rates in the UK are relatively low, stomach cancer is still the third highest cause of cancer mortalities worldwide. The largest risk factor for stomach cancer is a chronic infection of the H. pylori bacteria. The contributions of other factors like diets high in salt, smoked foods, smoking and obesity are also important.

H. pylori can be found in the gut, and some strains cause gastritis & stomach ulcers. Long term colonisation can result in persistent cellular and tissue damage. Over time, the damaged gut lining can lose its structure and eventually become so undefined that the patient develops atrophic gastritis – a precancerous condition that could eventually lead to cancer.

A to F shows the increasing change of structure to existing gastric epithelium, as a result of prolonged H. pylori infections. (A) The normal gastric epithelium is organised in invaginations called glands. (B) A remarkable increase in size is observed in the inflamed stomach after H.pylori infection, a condition called chronic gastritis. (C) Atrophic gastritis, a precancerous condition with a higher chance of leading to cancer: the glandular structure is lost. (D) The emergence of a new type of gland with different features: a condition known as intestinal metaplasia to cancer. (E-F) The progression from dysplasia to cancer. Credit: Correa & Piazuelo, 2013

 

Understanding how persistent infection can result in increased risk of cancer is the focus of Dr Francesco Boccellato, Ludwig Institute, and his lab. Improving the knowledge of underlying mechanisms in early cancer biology may help us to understand how cancers originate in various parts of the body, and thus giving doctors more insight to detect cancer earlier in patients with precancerous conditions.

Francesco’s most recent project is investigating the role of growth factors in the determination of gut epithelial cells. The cellular lining of the gut, known as the epithelium, is where most stomach cancers originate. The epithelium is made up of a variety of different types of cells, responsible for different things such as mucus secretion, production of gastric acid and digestive enzymes.

Cross section of the stomach lining showing a gastric gland with different cell types that make up the epithelium. What causes stem cells to differentiate into these different cells is the focus of the Boccellato lab. Credit: Boccellato lab

The team are investigating what it is that activates stem cells to differentiate into different epithelial cells, in the hope of identifying new ways that the cells can become cancerous.

It is Francesco’s hypothesis that the specific localisation of growth factors in the tissue microenvironment may be responsible for the differentiation process. If this is the case, then it may be that a change in the relative quantities or localisation of these growth factors triggers a change in the epithelium structure and cellular composition over time.

The team are investigating this through in vitro models known as mucosoid cultures – growing human epithelial cells outside of the body and exposing them to different conditions to see how the cells regenerate and differentiate. Mucosoids are an innovative stem cell based cultivation system developed by the Boccellato lab, which enables an exceptional long term regeneration and maintenance of epithelial cells. The cells form a polarised monolayer producing mucus on the top side similar to the epithelium in a patient.

Top: example of a mucosoid with cells (the plasma membrane is labelled in green) producing protective mucins (MUC5AC) labelled in red (the yellow is where the two labels overlap creating the mucus layer). Bottom: example of a mucosoid with cells (the plasma membrane is labelled in red and the nuclei in blue) showing one cells producing Pepsinogen (in green) the precursor of pepsin, the main digestive enzyme. Source: Boccellato et al., GUT 2019

The results of Francesco’s investigation into the role of growth factors in determining gut cell differentiation and progression into atrophic gastritis are expected in Spring 2021. It is hoped that by better understanding the role of growth factors underlying the epithelial structures in pre-cancerous conditions, we can detect when cancers may appear and thus treat them earlier. Further studies will elucidate the role of bacterial infections (like H.pylori) in this process of re-shaping the tissue.

The H. pylori-cancer relationship is a great model for understanding other infection-based cancers. Colon cancer, gallbladder cancer, cervical cancer, stomach cancer and lymphoma are all examples of cancers that can be caused by bacterial infection. By better understanding how gut tissues work and progress to pre-cancerous conditions, we can apply this to other cancer models to see if the same is true.

A final line of investigation by the team will be into how H. pylori bacteria access gut cells to cause damage. The epithelium is usually protected by a mucus barrier, on which our natural and harmless microflora grow. Healthy gut bacteria cannot perforate this mucus barrier to reach epithelial cells, but H. pylori appears to be able to. Francesco is investigating what makes this possible, so that we may be able to develop drugs that prevent H. pylori infections from reaching the epithelium and causing damage.

About the Boccellato lab

The Boccellato lab is investigating oncogenic pathogens and how they contribute to cancer. Patients infected with those pathogens have a higher chance of developing cancer, but the malignancy arises many years after the initial infection event. Cancer may develop as a result of a long battle between the pathogen that persists, hides and damages the tissue, and the host that attacks the pathogen and continuously repairs the damage caused by the infection.

The team use innovative tissue culture systems of human primary cells to re-build the infection niche in vitro and to understand the long term effect of infection on epithelial cells.  

References

Boccellato F.  GUT. 2019 Mar;68(3):400-413. doi: 10.1136/gutjnl-2017-314540. Epub 2018 Feb 21.

Sepe LP, Hartl., mBio. 2020 Sep 22;11(5):e01911-20.doi: 10.1128/mBio.01911-20.

Boccellato F, Meyer F. Cell Host Microbe. 2015 Jun 10;17(6):728-30.doi: 10.1016/j.chom.2015.05.016.

Piazuelo MB, Correa P. Gastric cáncer: Overview. Colomb Med (Cali). 2013;44(3):192-201. Published 2013 Sep 30.

 

Bowel cancer patients going undiagnosed due to COVID distruption

A new study led by the University of Oxford has found that since the first coronavirus lockdown the number of people diagnosed with bowel cancer in England has fallen sharply, with a deficit persisting up to October 2020.

Between April and October 2020, over 3,500 fewer patients than expected were diagnosed with bowel cancer in England. Since bowel cancer is more likely to be curable if it is detected at an early stage, these results suggest that many patients, whose diagnosis has yet to be made, may die unnecessarily. The results are published today in The Lancet Gastroenterology & Hepatology.

The research was carried out by a team of clinicians and academic researchers from across the UK, including from the University of Leeds and the University of Newcastle.

For this study, the researchers assessed the patterns of referral for bowel cancer investigation, diagnosis and treatment within the English NHS from 1 January 2019 to 31 October 2020.

The results showed that, compared with an average month in 2019, during April 2020 at the peak of the first wave of coronavirus:

  • the monthly number of referrals by GPs to hospital clinics for investigation of possible bowel cancer reduced by 63% (from 36,274 to 13,440);
  • the number of colonoscopies performed fell by 92% (from 46,441 to 3,484); and
  • the monthly number of people with confirmed bowel cancer referred for treatment fell by 22% (from 2,781 to 2,158), and the number of operations performed fell by 31% from (2,003 to 1,378).

This is the first study to assess the impact of the COVID-19 pandemic on the diagnosis and management of bowel cancer across England.

Full story available on the Nuffield Department of Population Health website.

“The Oxford Classic” classification system uncovers new information about ovarian cancers

In 2020, using single cell RNA sequencing, Oxford cancer researchers made a breakthrough by identifying  new types of Fallopian tube cells that are the cells of origin for the majority of ovarian cancers. They showed that that the types of these newly-discovered non-cancer cells are “mirrored” into different ovarian cancer subtypes. These subtypes correlated well with survival.

Discovering the new subtypes of cells have allowed Oxford researchers to classify and categorise tumours based on their origin in the body, and determine which ones can lead to more severe cancer outcomes – an approach which has been dubbed the ‘Oxford Classification of Carcinoma of the Ovary’ or ‘Oxford Classic’ for short. The Oxford Classic will provide much more accurate predictions for disease outcome in patients, as well as helping researchers to develop targeted therapies for each type of cancer

Professor Ahmed Ahmed, Nuffield Department of Women’s and Reproductive Health and originator of the Oxford Classic, has how published a paper in collaboration with Imperial College, demonstrating the applications of the Oxford Classic approach. As well as shedding light on some previously unknown information about ovarian cancers.

Professor Ahmed says:

“Our group is very excited that we were able to confirm the predictive role of the Oxford Classic. This work highlights that it is now important to identify new personalised therapies for the Oxford Classic-defined EMT-high ovarian cancer subtype. The finding that there is a strong connection with abundant M2 Macrophages already offers a good hint as to where we could find good treatment options for patients with this type”.

Serous ovarian cancer (SOC) is the most common cancer subtype, but is challenging to classify and predict its prognosis. Using the Oxford Classic, researchers found that specific SOC subtypes, known as EMT-high types, were associated with a lower survival rate in serous ovarian cancer patients.

Professor Christina Fotopoulou of Imperial College London says:

“This has been a very fruitful collaboration between two major UK gynaecological cancer centres; Oxford and Imperial College. We have generated very promising results towards an individualisation of care of our ovarian cancer patients. Our data will help clinicians to stratify patients to the right treatment pathway based on features of tumour biology of their disease. I hope we can continue to work together on that basis and expand and validate our data further also on a larger scale.”

EMT stands for epithelial-mesenchymal transition, it is the process by which epithelial cells change and become more mobile. This mobility provides the cells with the opportunity to spread leading to cancer progression. EMT-high subtypes are tumours that have a high number of cancer cells with greater mobility.

Researchers also found that EMT-high subtypes were associated with abundance of a type of immune cells called M2 macrophage. M2 macrophages possess immunosuppressive properties, and can lead to poorer treatment responses if they are found in high quantities within a tumour. It has previously been observed that patients with high-EMT tumours had a poor immune response. This study confirms that the EMT-high subtypes are associated with an immunosuppressive environment (and so poor patient responses to treatment) due to their association with more M2 macrophages – a link that has not previously been identified.

Whether M2 macrophages induce the EMT level or the EMT level results in higher levels of M2 macrophages will be an important question to be addressed by Prof Ahmed’s future work. However, this study has demonstrated the Oxford Classic’s strong ability to predict a patient’s prognosis.

Classifying the EMT status of a tumour, using the Oxford Classic, could potentially become a valuable part of future cancer stratification methods. This will ensure that appropriate treatment methods and attention are given to patients with a poorer overall prognosis.

Ovarian Cancer Action’s CEO, Cary Wakefield, says

“While other cancers have achieved major improvements in treatment outcomes, ovarian cancer continues to go unrecognised, underfunded, and misdiagnosed. The Oxford classic is an exciting breakthrough that will help to identify new treatment options for ovarian cancers that have a lower chance of survival. Funding important research like this will bring us closer towards a shared goal of more women surviving ovarian cancer”.

About the study

This study was co-led by Prof Ahmed Ahmed of the University of Oxford and Prof Christina Fotopoulou of Imperial College. It was funded by Ovarian Cancer Action, CRUK Oxford Centre and the National Institute for Health Research (NIHR) Biomedical Research Centre.

This study has demonstrated the potential of the Oxford Classic to:

  1. Accurately classify types of serous ovarian cancers
  2. Identify populations of cancer cells that have poorer prognoses (such as EMT high cancers)

Ahmed Ahmed is a Professor of Gynaecological Oncology at the Nuffield Department of Women’s & Reproductive Health at the University of Oxford and a Consultant Gynaecological Oncology Surgeon at the Oxford Cancer and Haematology Centre. His work focuses on surgical, medical and fundamental research into ovarian cancer, its early detection, treatment and screening.

Read the fully study here: http://clincancerres.aacrjournals.org/content/early/2021/01/12/1078-0432.CCR-20-2782

SCALOP team discover new pancreatic cancer biomarker

The discovery of pancreatic cancer biomarkers (naturally occurring molecules, genes or characteristics which can be used to confirm the presence or predict the outcome of a cancer) is vital in understanding patient outcomes and finding new therapeutic targets. In recent years, improved understanding of the biology of pancreatic cancers has resulted in new combination therapies being developed, including the development of the first successful biomarker-guided therapy in pancreatic cancer known as the POLO trial.

A recent paper from the SCALOP-1 trial team, led by Prof. Somnath Mukherjee, was published in BJC Nature, which has identified proteins that could act as a new biomarker to predict a patient’s outcome from pancreatic cancer. The chemokine protein known as CCL5, found circulating in patient blood, was found in low quantities in patients with better overall pancreatic cancer survival (around 18.5 months, rather than less than a year).

It is already known that CCL5 is involved in tumour invasion, tumour metastasis and the creation of an immune-system-suppressing micro-environment that allows pancreatic cancer to develop quickly. Its identification as a biomarker makes CCL5 a perfect new target for potential drug treatments. For example, blockade therapies that target the CCL5-CCR5 pathway and reduce the presence of CCL5, may produce new opportunities to improve the outcome of other immunotherapies that pancreatic cancer patients are undergoing.

Co-lead of this study, Prof Eric O’Neil from the Department of Oncology, is now investigating combination of CCL5 antagonist drugs with immunotherapy and radiotherapy drugs in animal models, which he hopes will lead to the development of new, more-effective pancreatic treatments in the future.

Next steps for the SCALOP trials

When pancreatic cancer has developed beyond a stage where it is operable, the only option for patients is often chemotherapy or chemoradiotherapy (the combination of chemo and radio therapy). The creation of new combination drugs used in the chemotherapy process has led to some improvement in overall length of patient survival of pancreatic cancer, which remains one of the highest causes of cancer death in the UK, however the use of these drugs is limited by the toxic effect on the body.

Following on from the SCALOP-1 trial, the SCALOP-2 trial, has been run from the University of Oxford, hosted through the Oncology Clinical Trials Office and lead by Prof Somnath Mukherjee. It has completed recruitment earlier in the year and final results are awaited.

Currently in the UK, chemoradiotherapy for locally advanced pancreatic cancer consists of 28 daily treatments of radiotherapy. Although this treatment is effective in controlling local symptoms and slowing down local cancer progression, in most cases it is unable to remove the cancer or shrink it well enough to make it operable. There is a need to find more efficient treatment combinations to improve patient outcomes.

The SCALOP-2 clinical trial compared different ways of combining chemotherapy and chemoradiotherapy to see which combination provides the most benefit to patients who have inoperable pancreatic tumours. This includes testing radiotherapy dose escalation and the use of nelfinavir as a radiosensitizer drug – something that makes tumour cells more sensitive to the effects of radiation therapy. In doing so, it is hoped that researchers can uncover more efficient drug combinations for patients with pancreatic tumours that are inoperable.

Blood and biopsy samples have been collected as a part of SCALOP-2 trial, in order to allow the team to take a more detailed look at proteins, DNA and cells involved in the cancer and how they are affected by treatment. This will tell researchers much more about how a patient’s type of cancer behaves and how it has responded to various treatments, allowing for the discovery of biomarkers just like CCL5 from the SCALOP-1 trial.

More information about the SCALOP-2 trial can be found on the Pancreatic Cancer UK website here.

New melanoma drug a step closer to the clinic

Previous phase 1 and 2 clinical trials have been conducted into Tebentafusp, a new anti-tumour immune response drug for patients with metastatic melanoma. The results from Immunocore and the University of Oxford, found that this first-of-its-kind treatment showed great promise in helping the immune system fight off melanoma cancers of both the eye and skin. The phase 3 clinical trial for this drug is the first for an affinity optimised T-cell receptor drug, making it the first of its kind.

Today, Immunocore the company behind the drug have announced trial results showing tebentafusp works better for patients with untreated metastatic uveal melanoma, when compared to other treatment choices.

“A positive survival benefit for tebentafusp represents a major step towards bringing a potential new treatment for cancer patients with a high unmet need. If approved, it would be the first new therapy to improve the overall survival in 40 years and to be specifically used in the treatment of metastatic uveal melanoma, a disease with poor survival where new therapies are urgently needed”

– Bahija Jallal, CEO of Immunocore

Tebentafusp comes out of clinical trials led by Prof Mark Middleton (Department of Oncology). Now, we see the potential for this drug coming into the clinic, subject to regulatory approval, as early as next year.

“It is very exciting that our observations in the first trial of tebentafusp, that it could make some uveal melanomas shrink, have now been borne out in larger studies. There’s still a way to go but there is every hope that this will prove an option for the treatment of this difficult cancer quite soon.”

– Prof Mark Middleton, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre.

Uveal melanoma is a rare and aggressive form of cancer that affects the eye, and typically has a poor prognosis and has no accepted optimal treatment and management. After the cancer metastases, 50% of patients have life expectancy of less than a year. Tebentafusp has the potential to be the first new therapy to improve the life expectancy of patients in over 40 years.

About the researchers

This research was funded by Immunocore.

Prof Mark Middleton is the Head of the Department of Oncology at the University of Oxford. He has overseen the development of internationally leading melanoma and upper GI clinical research groups and establishment of portfolios of early phase radiotherapy and haemato-oncology trials in Oxford. He is involved in the evaluation of novel immunotherapeutics, including pre-clinical development, trial design, proof of mechanism and proof of concept.

Immunocore, is a pioneering, clinical-stage T cell receptor biotechnology company working to develop and commercialise a new generation of transformative medicines to address unmet needs in cancer, infection and autoimmune diseases.  The Company’s most advanced programs are in oncology and it has a rich pipeline of programs in infectious and autoimmune diseases. Immunocore’s lead program, tebentafusp (IMCgp100), has entered pivotal clinical studies as a treatment for patients with metastatic uveal melanoma. Collaboration partners across the Immunocore pipeline include Genentech, GlaxoSmithKline, AstraZeneca, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Immunocore is headquartered at Milton Park, Oxfordshire, UK, with offices in Conshohocken, Pennsylvania and Rockville, Maryland in the US. For more information, please visit www.immunocore.com.

The National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) is based at the Oxford University Hospitals NHS Foundation Trust and run in partnership with the University of Oxford.

The NIHR is the nation’s largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata