For the first time, an experimental vaccine designed not to treat existing cancer but to prevent it from appearing has just obtained the green light from the British authorities. In the United Kingdom, the Medicines and Healthcare products Regulatory Agency has authorized a phase 1/2 trial in people carrying the
Lynch syndromea genetic abnormality that affects about one in 300 people and carries the risk of cancer up to 80%.
Lynch syndrome: an extraordinary cancer risk
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Lynch syndrome is an inherited predisposition where genes responsible for repairing DNA malfunction. Errors accumulate in cells, which can develop into precancerous lesions and then tumors. According to the University of Oxford, this condition affects around one in 300 people and can bring the overall risk of cancer up to 80% over a lifetime.
Moderna data indicates that a carrier can have up to an 80% risk of colorectal cancer and 60% of endometrial cancer, with also an excess of ovarian, stomach, pancreatic or prostate cancers, often before the age of 50.
“While the lifetime risk of developing colorectal cancer is approximately 5% in the general population, it is around 40% in Lynch syndrome“, told us Dr Chrystelle Colas, head of the Clinical Genetics Unit at the Institut Curie. “The risk is lower but remains significant for all organs making up the tumor spectrum: ovaries, stomach, small intestine and urinary tract.“, adds Dr Colas.
Lynch syndrome accounts for approximately 3% of colorectal and endometrial cancers. Prevention is mainly based on frequent colonoscopies, a pelvic ultrasound from the age of 35, a fibroscopy every 4 years, or even annual monitoring of the urinary tract, sometimes associated with aspirin and surgery.
How the mRNA-4194 vaccine aims to neutralize “pre-cancer”
The vaccine mRNA-4194 contains a messenger RNA that instructs cells to make protein fragments typical of precancerous cells linked to Lynch syndrome. The immune system then learns to recognize them and destroy them before a tumor appears.
“The INTERCEPT-Lynch trial represents a significant step forward in our efforts to prevent cancers associated with Lynch syndrome before they even appear. By using mRNA vaccine technology to train the immune system to recognize precancerous lesions, or what we call “precancerous”, we hope to reduce the risk of cancer and ultimately improve the quality of life of people with this inherited disease,” explains Professor David Church, senior cancer researcher at the Center for Human Genetics. the University of Oxford.
The trial, funded by Moderna and coordinated by the Oncology Clinical Trials Office at Oxford with support from Oxford Cancer, will measure vaccine safety, dose and immune response in previously diagnosed adults. The requirements were discussed with patients. “Despite the availability of risk-reducing interventions, the reality and fear of cancer remains significant for people with Lynch syndrome. This research has the potential to be a game-changer, offering real hope for a future with less fear of cancer“, summarizes Helen White, a Lynch syndrome carrier involved in the design of the study.
The first injections are expected in the summer in Oxford, before a phase 2 open to other British centers planned for 2027.
A first in the prevention of hereditary cancers, still far from everyday life
In Oxford, INTERCEPT-Lynch is part of a precision prevention program that tests targeted treatments in very high-risk groups. This first trial remains early and limited in the United Kingdom, without proof of clinical effectiveness for the moment, but it already opens a new avenue for families affected by Lynch syndrome.