A new cancer vaccine trial targeting bowel and ovarian cancer in at-risk individuals is set to begin this summer, with the first patients expected to receive an experimental mRNA jab designed to prevent the diseases from ever developing.
The INTERCEPT-Lynch Trial
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has authorised a Phase 1/2 study of the investigational vaccine, designated mRNA-4194, for people with Lynch syndrome – a genetic condition that dramatically raises the risk of several cancers. The trial, named INTERCEPT-Lynch, is a collaboration between the University of Oxford and the pharmaceutical company Moderna, with backing from Cancer Research UK. It marks Moderna’s first venture into cancer prevention using its mRNA technology.
The initial phase will assess the vaccine’s safety, characterise the immune response it generates, and determine the optimal dosage. The study is funded by Moderna and sponsored by the University of Oxford. A second, expansion phase involving multiple centres across the UK, including Oxford, is anticipated to begin in 2027.
This trial forms part of a broader 10-year strategic partnership between Moderna and the UK Government, established in 2022 to strengthen the country’s mRNA capabilities and pandemic preparedness. Under that partnership, more than 20 clinical trials have already been delivered across 135 centres, involving over 14,500 participants. The Moderna Innovation and Technology Centre (MITC) in Harwell, Oxfordshire, opened in September 2025 as part of the same collaboration.
What is Lynch Syndrome?
Lynch syndrome affects approximately one in 300 people in England, equating to around 175,000 individuals. Yet fewer than 5 per cent are aware they carry the condition. It is caused by inherited mutations in genes responsible for DNA repair – specifically the mismatch repair genes MLH1, MSH2, MSH6, PMS2, and EPCAM. These mutations allow DNA errors to accumulate, making cells far more likely to become cancerous.
The syndrome significantly elevates the lifetime risk of developing bowel cancer – by around 80 per cent – and accounts for roughly 1,100 bowel cancers in England each year. It also sharply increases the risk of womb (endometrial) cancer and ovarian cancer in women, as well as stomach, pancreatic, kidney, skin, urinary tract, and brain cancers. Currently, management options for people with Lynch syndrome are limited to regular surveillance, with low-dose aspirin and, in some cases, surgery used as preventive measures.
How the mRNA Vaccine Works
The INTERCEPT-Lynch trial aims to train the immune system to identify and eliminate pre-cancerous cells before they develop into full-blown tumours. Professor David Church, a Cancer Research UK senior cancer research fellow at the University of Oxford and the study’s lead investigator, described the mRNA jab as an “instruction manual” for the body.
In people with Lynch syndrome, faulty DNA repair leads to a build-up of mutations. These mutations can make cells increasingly abnormal, but they also create distinctive molecular markers that the immune system can be taught to recognise. The vaccine delivers messenger RNA instructions that prompt the body to produce proteins found on these pre-cancerous cells. With sufficient stimulation, the immune system learns to attack and destroy the abnormal cells, halting cancer before it starts.
Professor Church noted that, as with many vaccines, patients may require a booster jab at some stage to maintain immunity. The targets chosen for the vaccine are shared across multiple cancer types associated with Lynch syndrome, meaning it should offer broad protection if it proves effective. He added that the vaccine could be “transformative” for Lynch syndrome patients, including those who have already suffered one type of cancer – a common scenario, as women with the condition often develop womb cancer and later bowel cancer, or vice versa.
Oxford experts believe the approach could eventually be adapted for other cancer types not linked to Lynch syndrome. Professor Church said that the proof of principle – demonstrating that the immune system can be trained to recognise cancer-associated alterations and prevent progression – “should give us insights that are generalisable”.
Other experimental vaccines for Lynch syndrome are also under investigation. An off-the-shelf immunotherapy called Nous-209 has shown promise in early-phase trials, and a separate vaccine, Tri-Ad5, is being tested at the Dana-Farber Cancer Institute. In parallel, the UK is exploring personalised mRNA cancer vaccines, where treatments are tailored to individual tumour genetics, through initiatives such as the NHS Cancer Vaccine Launch Pad. Those trials cover bowel, melanoma, lung, and pancreatic cancers.
David Berman, chief development officer at Moderna, said: “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.”