Advancements in Lynch Syndrome Vaccine Research
Dr. Stacy Norton experienced the loss of her mother to colon cancer when she was only 7 years old. Several family members faced aggressive tumors at early ages. Now, Dr. Norton participates in testing a novel vaccine aimed at protecting against cancer for her and her children.
About 1 million Americans have Lynch syndrome, a genetic condition elevating the risk of colorectal and other cancers. This faulty gene necessitates annual colonoscopies to detect and remove precancerous polyps. Scientists are now focusing on vaccines that teach the immune system to stop colon cancer development before tumors form.
Three potential Lynch syndrome vaccines are under development, with clinical trials in the U.S. and Britain. The vaccine trial Dr. Norton joined has shown promising results, prompting Dr. Eduardo Vilar-Sanchez from MD Anderson Cancer Center to plan a larger study. Dr. Norton, now 59, remains hopeful that this vaccine could reduce her children’s need for frequent colonoscopies.
Lynch syndrome arises from an inherited genetic mutation. Typically, mismatch-repair genes act as DNA spellcheckers, correcting errors during cell multiplication. In Lynch syndrome, these corrections falter, leading to tumor developments, frequently emerging before age 50.
Colorectal cancer is a prevalent consequence of Lynch syndrome. The average person’s risk is 5%, while Lynch carriers face a risk up to 80%, as indicated by Vilar-Sanchez. This syndrome also raises the likelihood of other cancers, including endometrial, pancreatic, stomach, ovarian, certain skin cancers, and brain tumors.
Dr. Norton learned of her Lynch syndrome diagnosis in her 40s, already aware of her familial cancer history. This discovery led to annual colonoscopies and a preventive hysterectomy, which uncovered early-stage cancer in her uterus.
Developing Vaccines Against Gene-Caused Cancer
Currently, vaccines like HPV and hepatitis B prevent infections that may lead to cancer. However, creating vaccines for gene-related cancers is more complex. These require the immune system to recognize proteins from the hundreds of mutations in Lynch-related tumors, according to Vilar-Sanchez.
In early trials, Dr. Norton and 44 participating Lynch carriers received a Swiss biotech Nouscom vaccine. This vaccine trains the immune system to recognize 209 abnormalities typically found in Lynch precancers, enhancing tumor-removing T cells. A year later, study results showed fewer precancerous growths and no advanced polyps.
Dr. John Marshall from Georgetown University, though not involved in the study, observed, “This early paper suggests that yeah, maybe we can stimulate the immune system further to counteract Lynch syndrome-spurred tumors.”
Since 2014, Dr. Norton has experienced polyp-free colonoscopies following vaccination. She is part of a group receiving a booster shot, with further data expected this fall.
In Britain, Oxford University researchers are starting preliminary tests of a similar vaccine using Moderna’s mRNA technology. Meanwhile, a larger study is underway to compare ImmunityBio’s Tri-Ad5 vaccine to a placebo, focusing on different cancer markers.
Lynch Syndrome and the Rise in Young Adult Colon Cancer
Approximately 158,000 colorectal cancer cases occur annually in the U.S., predominantly affecting those over 50. However, cases in younger adults are rising, though the reasons remain unclear.
Lynch syndrome impacts around 1 in 279 individuals. While many are unaware, increased genetic testing promotes awareness, especially for those with family cancer history or early-age tumors.
Routine colorectal cancer screening is recommended starting at age 45. Yet, symptoms like blood in the stool, changes in bowel habits, unintended weight loss, and abdominal pain warrant immediate medical attention.
The Associated Press Health and Science Department, supported by the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation, retains full content responsibility.