A New Vaccine Can Prevent the Return of Melanoma. Will It Work on Other Cancers?

Pharmaceutical companies Merck and Moderna released new data showing that their experimental mRNA cancer vaccine prevented the return and spread of melanoma, the deadliest form of skin cancer. The results of the Phase 3 clinical trial were announced on October 24 at the annual meeting of the European Society for Medical Oncology in Madrid. Of the study subjects who received the vaccine, 82.2 percent had survived without a relapse after two years, versus only 70 percent of those in the control group—amounting to a 42 percent reduction in death or cancer recurrence compared to the standard treatment. In addition, the risk of metastasis—when cancer cells spread to other parts of the body—was also lower in patients who received the vaccine as opposed to those who received standard care.

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

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Side effects were minimal as well. These included fatigue, fever, and some pain at the injection site, all typical of viral vaccines, according to the researchers. “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.

As the companies first announced in August, these results mean the drug has 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.

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.

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. Now that the results of the trial are in, Moderna and Merck will seek U.S. approval for the vaccine. Mehnert says the FDA will now evaluate the data, and if the agency agrees that they are convincing and worthwhile, then the team will begin scaling the vaccine for global use. “We’re very prepared to do that,” she adds.

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It’s less certain how or whether this success will translate to other types of cancers. In a paper published in Nature Medicine in October, Wu’s team reported the Phase 1 trial results of a similar vaccine for ovarian cancer. The results were mixed. Though the vaccine did boost immune responses in some patients, it was not as successful at preventing relapses, indicating that there is still a lot of work to be done before the approach is useful for a wide variety of cancers.

It’s also unclear why the vaccine was so effective. While acknowledging that these results “mark a crucial moment in the field of cancer vaccines,” Inge Marie Svane, cancer immunologist at Copenhagen University in Herlev, Denmark, who spoke at the conference, pointed out that the neoantigens themselves might not the source of the success, but rather the mRNA or the lipid nanoparticles might be responsible for the benefits.

Still, for melanoma patients, the news is undoubtedly good. 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.”