The trial forms part of a scientific collaboration between the University of Oxford and Moderna to advance a novel mRNA approach to cancer prevention. Led by Professor David Church, Cancer Research UK Senior Cancer Research Fellow in the University of Oxford’s Centre for Human Genetics in the Nuffield Department of Medicine, it will test ‘mRNA-4194’, an investigational mRNA-based vaccine developed by Moderna, which is designed to help prevent cancer in people with Lynch syndrome (LS).
LS is an inherited condition that affects around one in 300 people worldwide, which causes lifetime cancer risk of up to 80%. People with the condition face elevated risks of several cancer types, including colorectal, endometrial, ovarian, stomach, pancreatic and prostate cancers.
mRNA-4194 is designed to leverage mRNA technology to train the immune system to recognise and eliminate pre-cancerous cells in LS before cancer develops. The trial will administer the vaccine to participants with LS to assess safety, characterise immune response and determine the optimal dose for further testing. It is anticipated that the first participant will receive the vaccine in Oxford this summer. A second phase of the trial, expected to begin in 2027, will expand recruitment to additional centres across the UK.
“People with Lynch syndrome live with a very high risk of developing cancer, often at a younger age than the general population. The INTERCEPT-Lynch trial represents a meaningful step in our efforts to prevent Lynch syndrome-associated cancers before they develop,” said Professor David Church. “By using mRNA vaccine technology to train the immune system to recognise early cancer changes, or what we call ‘pre-cancer,’ we hope to reduce cancer risk and ultimately improve the lives of people with this inherited condition.”
The trial is the culmination of three years of dedicated research into preventative treatments for LS-associated cancers in Oxford, involving a multidisciplinary team spanning the Nuffield Department of Medicine, the Department of Oncology, the MRC Weatherall Institute of Molecular Medicine and Oxford Cancer. Key contributors to the programme include Professor Ellie Barnes, who is the Clinical Trial Lead for the immunological work, Professor Tim Elliott, Dr Eleni Adamopoulou and Dr Robert Watson. Dr Watson*, who leads the translational work underpinning the study, also played a key role in establishing the trial alongside Professor Church.
Through Oxford Cancer, the trial was also designed in close collaboration with people with LS, to ensure that the trial requirements would not place an excessive burden on patients.
Helen White, who was diagnosed with endometrial cancer and later LS in her early 50s, has been involved in consultations on the trial design from an early stage. Reflecting on her experience, she said:
“It’s been a privilege to contribute to the design of this trial as part of the INTERCEPT-Lynch Public and Patient Involvement Group. Drawing on our own experiences as people living with Lynch syndrome, including undergoing colonoscopies, has helped ensure the study is both participant-focused and shaped by real-world experience. Despite the availability of risk-reducing interventions, both the reality and fear of cancer remain significant for people with Lynch syndrome. This research has the potential to change that, offering real hope for a future with less fear of cancer.
Commenting on the news, David Berman, Moderna’s Chief Development Officer said:
“This MHRA authorisation marks an important milestone as we explore approaches to shift cancer care from treating disease to preventing it. By applying mRNA technology earlier in the patient journey, we aim to harness the immune system when it can have the greatest impact. We are proud to bring this innovation to the UK, building on our long-standing collaboration with leading UK institutions to advance mRNA research and development. We are deeply grateful to the participants, investigators and partners who make this research possible.”
The Lynch prevention research programme in Oxford was first funded through the Oxford Cancer Immuno-Oncology Network. It was later supported by Cancer Research UK, in a grant that was co-coordinated through the Oxford Centre for Cancer Early Detection and Prevention.
*Dr Watson is funded by the NIHR and the CRIS Cancer Foundation