Early-stage vaccine trials aim to prevent colon cancer in people with Lynch syndrome genetic mutation
Scientists are testing vaccines designed to prevent colorectal cancer in people with Lynch syndrome, an inherited genetic mutation affecting an estimated 1 million Americans that can raise colon cancer risk to as high as 80%. At least three potential Lynch syndrome vaccines are in development, including two in early clinical trials in the United States and a third beginning in Britain. A first-step study published in Nature Medicine found that one vaccine reduced precancerous growths and produced no advanced polyps in participants one year after vaccination.
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Lynch syndrome is caused by a mutation in so-called mismatch-repair genes — genetic "spellcheckers" that normally correct DNA errors arising when cells divide. When those genes malfunction, abnormalities accumulate and can lead to tumors, often before age 50. Colorectal cancer is the most common consequence, but Lynch carriers also face elevated risks of endometrial, pancreatic, stomach, ovarian, and certain skin cancers, as well as some brain tumors.
In a first-step study, 45 Lynch carriers tested a vaccine developed by Swiss biotech Nouscom that teaches the immune system to recognize 209 abnormal proteins associated with Lynch-related precancers. The approach revved up tumor-eliminating T cells, and colonoscopies a year later showed fewer precancerous growths and no advanced polyps, according to results published in Nature Medicine. Lead researcher Dr. Eduardo Vilar-Sanchez of MD Anderson Cancer Center said the results are promising enough that a larger follow-up study is expected to begin early next year.
Two additional vaccine candidates are also moving forward. Oxford University researchers are beginning initial testing of a vaccine made by Massachusetts-based Moderna using the mRNA technology behind its COVID-19 shot. Separately, scientists are awaiting results from a study comparing California-based ImmunityBio's Tri-Ad5 vaccine — which targets a different set of cancer markers — against a placebo.