Why Scientists Say This Personalized Cancer Vaccine Could Be a Game-Changer

An experimental mRNA cancer vaccine prevented the return and spread of melanoma, the deadliest form of skin cancer, in a large clinical trial, pharmaceutical companies Merck and Moderna announced this week.

The companies said the drug had successfully met the primary goal of its Phase 3 clinical trial, the last step necessary before requesting approval from the U.S. Food and Drug Administration. This is the first time an mRNA cancer vaccine has gotten this far.

The trial included over 1,000 melanoma patients whose tumors had been removed but were at risk of their cancer returning. It compared a combination of intismeran, a personalized cancer vaccine, and Keytruda, a monoclonal antibody that is commonly used to prevent melanoma recurrence, against administering Keytruda alone.

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Though the companies haven’t yet released their data, they said that an interim analysis of the results showed that the combination was more effective and only had minimal side effects, including fatigue and fever.

“Patients felt crummy for a few days and missed a day or two at work, but nothing life-threatening,” said Janice Mehnert, cancer physician and researcher at NYU’s Perlmutter Cancer Center and lead investigator on the study.

This study shows that the method, which researchers have been developing for almost a decade, is actually helping patients, says Catherine Wu, a physician and researcher at Harvard’s Dana-Farber Cancer Institute, whose team first demonstrated proof of concept for mRNA vaccines in 2017. Wu adds that “the odds are good” that this type of vaccine will work for other types of cancer as well.

“If this does work in other cancers—and it’s already being tested in bladder and lung cancer—it could be a real game-changer,” Mehnert adds.

A Cancer Treatment Just for You

Traditional cancer therapies have been one-size-fits-all treatments. But these mRNA cancer vaccines, also known as neoantigen therapy, target the specific cancer cells of a specific patient.

“It's not like making an arsenal of one type of vaccine that you give to a bunch of patients,” Wu explains. “You are actually creating bespoke vaccines for each individual.”

Researchers start by taking a sample of a cancer tumor, either by biopsy or removing the cancer entirely, sequencing its DNA, and comparing it to the DNA of healthy tissue from the same person. By doing so, researchers can spot the mutations that are causing the cancer. Machine learning algorithms then help predict which neoantigens—molecules produced by the mutation—are most responsible for your particular tumor.

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Next researchers need to figure out how to tell your immune system where to find those neoantigens. Just like each person’s cancer is unique, so is their HLA type—or human leukocyte antigens, protein markers found on almost all cells of the body. These proteins are what tip off your immune system to which cells it should kill.

With this information in hand, researchers are able to design a personalized vaccine. They create a molecule of mRNA, a type of RNA that carries genetic instructions, and encode it with instructions that tell your immune system how to attack your tumor. The molecule is wrapped in a lipid nanoparticle and injected, just like a flu shot.

“You're trying to give the immune system a blueprint, like a roadmap of what to look for and how to get rid of it,” Mehnert explains.

‘The Future Is Incredibly Exciting’

The researchers are expected to present their data soon, but the results are likely similar to the Phase 2 trial published this June, which demonstrated the vaccine lowered the risk of recurrence or death by 49 percent. The only major differences, Mehnert says, were that the Phase 3 trial included far more people and did not focus only on late-stage cancer patients.

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Phase 3 trials are very useful for finding new standards of care because the size of the pool of subjects allows researchers to compare outcomes among different groups of patients. The next step, Mehnert says, is for the FDA to evaluate the data, and if they agree that they are convincing and worthwhile, then the team will move begin scaling this for a global approach. “We’re very prepared to do that,” she added.

Nina Bhardwaj, director of immunotherapy at the Icahn School of Medicine at Mount Sinai who is behind a great deal of the basic research that led to this new vaccine, says this treatment could be “revolutionary” for patients who’ve had their tumors removed but are still at risk of their cancer returning, she says. “I think the future is incredibly exciting.”