Can mRNA vaccines be used in cancer care?

The COVID-19 vaccines mark the first widespread use of mRNA technology. They work by using synthetic genetic code to instruct the patient’s cells to recognize the coronavirus and activate the immune system against the virus.

But researchers began exploring how to use mRNA vaccines as a new way to treat cancer long before this technology was used against the coronavirus.

“We've known about this technology for a long time, well before COVID-19,” says Van Morris, M.D. Here, he explains how mRNA vaccines work and how a team of MD Anderson colorectal cancer experts led by Scott Kopetz, M.D., Ph.D., are testing the technology in a Phase II clinical trial.

What is mRNA?

Messenger RNA – known as mRNA – are genetic instructions for our cells. “mRNA serves as a code to make proteins,” Morris says. Proteins are needed for cellular functions inside our bodies, including growth, energy production and defense against illnesses.

mRNA technology is a strand of mRNA created in a lab that prompts the recipient’s cells to create protein fragments that are based on the “non-self” DNA characteristics of the vaccine’s target. When recognized, the protein fragments trigger a response from the patient’s immune system. “The protein fragments created from the mRNA signal are recognized by the immune system as foreign,” Morris says. “The immune system kills those cells and says, ‘I'm going to see if I can find any other cells in the body with these foreign proteins and kills those, too.’”

In the case of the COVID-19 vaccines, the mRNA causes the recipient’s cells to produce the spike protein from the SARS-CoV-2 virus. The immune system then recognizes the spike as “not self” and produces another type of protein called antibodies. These defend the body against the coronavirus.

Could mRNA technology prevent colorectal cancer recurrence?

A team of international researchers is working to test whether mRNA technology could prevent colorectal cancer from recurring.

The standard treatment for many colorectal cancer patients is surgery, but cancer cells can remain in the body after the tumor is removed. These remaining cancer cells shed DNA into the bloodstream, which is referred to as circulating tumor DNA (ctDNA).

A clinical trial led by Morris and Kopetz is following high-risk patients with stage II or stage III colorectal cancer who test positive for circulating tumor DNA after surgery.

The presence of circulating tumor DNA is checked with a blood test. “If there is ctDNA present, it can mean that a patient is at higher risk for the cancer coming back,” Morris says.

He says that the opposite can also be true: if there is not circulating tumor DNA present, the patient may have a lower risk of recurrence.

Personalizing an mRNA vaccine for mutations that cause cancer

In the Phase II clinical trial, enrolled patients start chemotherapy after the tumor is surgically removed. Tissue from the tumor is sent off to a specialized lab, where it’s tested to look for genetic mutations that fuel the cancer’s growth.

Morris says anywhere from five to 20 mutations specific to that patient’s tumor can be identified during testing. The mutations are then prioritized by the most common to the least common, and an mRNA vaccine is created based on that ranking. “Each patient on the trial receives a personalized mRNA vaccine based on their individual mutation test results from their tumor,” Morris says.

As with the COVID-19 vaccines, the mRNA instructs the patient’s cells to produce protein fragments based off tumor’s genetic mutations identified during testing. The immune system then searches for other cells with the mutated proteins and clears out any remaining circulating tumor cells.

“We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” says Morris.

A leader in circulating tumor DNA

MD Anderson researchers are hopeful for the future of circulating tumor DNA. “It’s an evolving technology,” says Morris. “It’s new and exciting, and we know it can help us predict which patients are at a high risk of recurrence.”

Morris says this clinical trial is one of many exploring this new approach. “MD Anderson is a world leader in colorectal clinical trials for ctDNA,” he adds. “No matter your stage of disease, we have a new trial potentially for you.”

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