The first participant has received an investigational vaccine that researchers hope will help to prevent cancer in people with Lynch syndrome (LS).
The INTERCEPT-Lynch trial, which is supported by the NIHR Biomedical Research Centre: Oxford, forms part of a scientific collaboration between the University of Oxford and Moderna to advance a novel mRNA approach to cancer prevention. Phase 1 of the trial got under way after receiving authorisation from the Medicines and Healthcare products Regulatory Agency.
LS is an inherited condition that affects around one in 300 people worldwide – or 175,000 people in the UK. They have an 80% risk of developing cancer in their lifetime and face an increased risk of several cancer types, including colorectal, endometrial, ovarian, stomach, pancreatic and prostate cancers.
The mRNA-4194 vaccine developed by Moderna is designed 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 the immune response and determine the optimal dose for the second phase, which is expected to begin in 2027 and include other centres in the UK.
The first patient to receive the vaccine, Sarah Ewart, 53, from Oxford found out she had Lynch Syndrome 24 years ago.
She said: “For people living with a higher risk of cancers, a preventative vaccine encouraging the body to spot and attack early cancers would be life changing. I’m excited to be in the first phase of this trial, and so grateful to the researchers and medical staff. I hope the trial is successful and becomes a massive leap forward in reducing cancers.”
The trial is 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. He said: “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.”
“By using mRNA vaccine technology to train the immune system to recognise early cancer changes – 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 number of University Oxford departments and institutes. Key contributors include BRC Oxford Deputy Director Professor Ellie Barnes, who is the Clinical Trial Lead for the immunological work, and Oxford BRC Cancer Theme Co-lead Professor Tim Elliott.
The trial was designed in close collaboration with people with LS, to ensure that the trial requirements would not place an excessive burden on patients. One of those involved in consultations on the trial design was Helen White, who was diagnosed with endometrial cancer and later LS in her early 50s.
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.”
People with LS are born with a variant in a gene that makes it harder for their bodies to repair mistakes when DNA copies itself – a process that happens in cells all the time. These mistakes, or mutations, can build up, making the cells containing them more likely to transform into cancerous cells.
The same mutations also make them more visible to the immune system, and with enough stimulation, the immune system can attack these abnormal cells and stop cancer from forming.
The Oxford researchers have identified several mutations occurring in the most common cancers associated with LS. These mutations appear very early in cancer development in people with LS, making them a good target for a preventative approach.