- Lynch syndrome greatly increases the risk of colon and other cancers, with some individuals facing up to a 74% chance of developing colon cancer.
- Dana-Farber researchers are testing a vaccine that trains the immune system to recognize and eliminate cancer cells before they develop.
- This clinical trial is the largest of its kind in North America and aims to transform cancer prevention for Lynch syndrome patients.
People with Lynch syndrome have an elevated risk of developing colon cancer and several other cancers. For example, someone without the inherited condition has about a 5% chance of developing colon cancer. But for someone with Lynch syndrome, it could be anywhere from 22% to 74%.
What if there were a way to reduce the risk of those cancers developing?
Dana-Farber researchers are running a clinical trial testing a cancer vaccine that trains the immune system to very specifically recognize the kinds of cancer cells that are likely to develop in people with Lynch syndrome — and eradicate them before they develop into cancer.
“We’ve been seeing incredible success with immunotherapies that harness the body’s immune system to fight cancers,” says gastroenterologist Ramona Lim, MD, who is leading the trial at Dana-Farber. “We’d like to use these same principles to prevent cancer from occurring in genetically predisposed individuals using a vaccine. It is a very exciting prospect.”
The study, which will assign participants randomly to receive either the vaccine or placebo, is offered through the Dana-Farber Lynch Syndrome Center for adults with Lynch syndrome who qualify.
What is Lynch syndrome?
Lynch syndrome is caused by an inherited mutation in one of five genes that are part of the instructions that control a process in cells that corrects “typos” in the genome. Mutations are alterations in the instructions that cause this process to be faulty and increase the chances of several cancers, most commonly colorectal cancer and uterine cancer, but also ovarian, urinary and biliary tract cancers, and skin tumors.
How does the vaccine work?
The Tri-Ad5 vaccine trains the immune system to recognize an enemy and attack. The immune system normally does this work on its own, but vaccines provide advanced and long-lasting training that helps the immune system’s T cells recognize cancer at its earliest stages and keep an eye out for cancer over a long period of time.
Tri-Ad5 combines three vaccines that expose the body to three different “tumor-associated antigens,” which are molecules that are commonly seen across many forms of cancer and are known to be able to trigger an immune response. The vaccine is also administered with an additional medicine that primes the immune system for learning about new antigens.
The Tri-Ad5 vaccine has previously been tested in a phase 1 clinical trial in a small number of patients with advanced cancers. The vaccine was safe and showed that the vaccine resulted in making the desired changes to the immune system, tuning it to recognize cancer cells with the three tumor-associated antigens. That trial provided evidence to support this larger phase 2 clinical trial, which aims to determine the vaccine’s effectiveness in participants with Lynch syndrome. Enrollment and initial follow-up of the safety phases of the trial has been completed. The study is now enrolling in the randomized controlled phase.
The Tri-Ad5 vaccine is based on vaccine delivery technology called Ad5. The U.S. Food and Drug Administration has approved one Ad5-based cancer vaccine for a form of bladder cancer. Tri-Ad5 and other Ad5-based cancer vaccines are still being investigated in clinical trials.
Who is eligible for the trial?
The trial is open to adults over age 18 with Lynch syndrome. Patients with Lynch syndrome and history of colon polyps or colorectal cancer can join the trial if they meet other entry criteria.
To defend against cancer, these patients currently have only screening or cancer prevention approaches that require taking medicines intended to lower the risk. This approach of using the body’s own defenses to lower the risk of cancer is different.
“This is the biggest vaccine prevention trial we’ve ever had in Lynch syndrome in North America,” says Lim. “We are really eager to learn if we can shift the paradigm in terms of what we can do for cancer prevention.”
What do patients in the trial need to do?
The trial is designed to fit seamlessly into the normal annual colon cancer screening schedule that people with Lynch syndrome are suggested to follow.
“Oftentimes folks in clinical trials have to go through extra procedures, but the way this trial is designed, they’re mainly just going through their annual exams,” says Lim. “Those
exams will show us whether this is a promising future direction for these patients.”
A patient wishing to enroll begins the process with regular colon cancer screening. If no cancer is found and the patient meets other criteria for inclusion, they receive either the vaccine or a placebo, which is a multi-step process requiring several visits. At the end of the next two years, they are screened for colon cancer again.
The trial is a randomized, double-blinded trial, meaning that neither the providers or the patients know who receives the vaccine or placebo, to remove biases that could influence the findings.
The researchers will use results from the colonoscopy screening to determine if the group receiving the vaccine developed cancer less frequently than the group that received the placebo. Samples taken will also help investigators learn if the vaccine stimulated the expected immune response.
“We don’t know if this will be the vaccine that becomes a new intervention or if it will be a different preventive approach in development,” says Lim. “But I’m finding that our patients are very excited to help us learn find the best new options for them and their families.”