Groundbreaking vaccine trial aims to prevent cancers associated with Lynch syndrome

LOS ANGELES - Groundbreaking vaccine trials aimed at preventing cancers associated with the genetic disorder Lynch syndrome are currently underway.

Lynch syndrome is a genetic condition that increases the risk of many kinds of cancer, according to the Centers for Disease Control and Prevention. 

People with Lynch syndrome are more likely to get colorectal cancer and other cancers, and at a younger age (before 50), including

• Uterine (endometrial),
• Stomach,
• Liver,
• Kidney,
• Brain, and
• Certain types of skin cancers.

Lynch syndrome causes about 4,300 colorectal cancers and 1,800 uterine (endometrial) cancers per year.

There are already vaccines that prevent certain types of cancers. These vaccines target viruses like hepatitis B, known for causing liver and cervical cancer as well as the HPV vaccine. 

But these historic and experimental vaccine trials targeted at treating individuals with Lynch syndrome, would potentially create the first vaccine that treats nonviral cancers. 

Lynch syndrome is currently the most common cause of hereditary colorectal cancer and people who inherit the condition have an estimated lifetime risk as high as 80% for developing cancerous growths, according to the National Cancer Institute Division of Cancer Prevention. 

About 1 in 279 individuals, an estimated 1.1 million people in the U.S. alone have Lynch syndrome. 

Eduardo Vilar-Sanchez, M.D., Ph.D., deputy chair of the department of clinical cancer prevention at MD Anderson Cancer Center, who is leading one of the trials, said his team is interested in understanding how colorectal cancer begins. That’s why they’re targeting Lynch syndrome. 

In order to do this, Sanchez’s team focused on a very specific population of people who are born with a genetic mutation that predisposes them to develop colorectal cancer over their lifetime. By better understanding this, he hopes they can develop better preventative strategies to fight these and possibly other types of cancers. 

The trial, which is currently in phase 1, is sponsored by the National Cancer Institute.

Why Lynch syndrome? 

Sanchez explained that patients with Lynch syndrome are born with a genetic defect in a gene that is involved in DNA repair. 

"What happens is that everytime one of our cells is dividing there is new synthesis of DNA and spontaneously in that process there are DNA errors. There are natural systems in our cells that are equipped to recognize that error and correct it so we don’t get mutations all the time," Sanchez explained. 

"What happens in patients with Lynch syndrome is that the genetic defect they are born with is in one of the genes involved in this process of self repair of DNA errors," he continued. 

This means that people with Lynch syndrome are more prone than others to replicate these DNA errors over their lifetime which means an increased risk of cancer. 

These DNA errors generate proteins in the body that aren’t found in normal human cells which develop into tumors. 

Sanchez explained that because these proteins are not normally found in human cells, to the body, they appear completely foreign. This makes these abnormal cells similar in concept to an infectious agent that the body could identify and terminate with the help of a vaccine. This is similar to the COVID-19 vaccine. 

"An infectious agent is foreign, these tumor cells are also foreign, because they are making all these novel proteins that we call neo-antigens and that is how they prime the immune system," Sanchez said. 

Because of this, Sanchez said Lynch syndrome creates the perfect context for developing vaccines that could target the molecular origins that develop tumors. 

What makes Lynch syndrome unique is that it doesn’t just develop colon cancer. Patients with this disorder can develop other forms of cancer which is why Sanchez and his team are optimistic that developing a vaccine for Lynch syndrome can help with other genetic disorders that also cause cancer. 

Not curing cancer but preventing it

Sanchez said that the key to ultimately defeating cancer lies in prevention. He believes that developing this vaccine will put the medical community on the right path toward preventative measures for the millions of people born with genetic disorders that can lead to cancer.

While humans have made spectacular progress in curing cancer through therapy, that in itself is a very difficult task and rarely achievable. 

"Development of preventative vaccines is not only going to help us impact the community of Lynch syndrome carriers by bringing them tools to prevent cancer and extend their healthy lives which is a number one goal of this effort, but also we’re going to learn much more on how to prevent other preventative vaccines that can impact other cancers and hopefully this experience will also translate in other genetic diseases," Sanchez said. "This is just the first step, this is just a phase 1 clinical trial."