Moderna's Personalized mRNA Cancer Vaccine Shows Promising Results in Early Trial

High angle view of syringe and mRNA vaccine multidose vial for cancer immunotherapy

Javier Zayas / Getty Images

Key Takeaways

  • Moderna shared data from a phase 2b clinical trial on a cancer vaccine to prevent recurrent melanoma.
  • The vaccine uses mRNA technology—the same platform that Moderna and Pfizer used to create their COVID-19 vaccines.
  • Personalized cancer vaccines prime the immune system to recognize a patient’s unique tumor signature, and to prevent recurrent cancer.

Moderna’s personalized cancer vaccine was shown to reduce the risk of recurrence in patients with stage 3 or 4 melanoma in a phase 2b clinical trial. This is the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial.

The company uses genetic information from a patient’s tumor to create a customized vaccine that targets their cancer cells. Unlike some other vaccines, which prevent diseases from occurring in the first place, this therapy bolsters the immune system of people who already have cancer so it can better fend off cancerous cells in the case of a relapse.

Moderna’s vaccine improves upon the efficacy of the drug Keytruda (pembrolizumab), the current gold standard for preventing recurrent melanoma. When given in tandem, Keytruda and the vaccine reduced the risk of recurrence or death by 44% compared with Keytruda alone.

“The goal for the personal cancer vaccine is to really harness the power of that patient’s immune system to fight their own tumor,” said Michelle Brown, MD, PhD, program lead for oncology at Moderna. “There’s power in people and there’s power in their immune systems.”

Moderna shared the news in a press release on Dec. 13 and said it will share the full results at an upcoming oncology medical conference.

What Is Melanoma?

Melanoma is the most serious form of skin cancer. In 2019, the most recent year for which U.S. data is available, more than 88,000 people were diagnosed with melanoma and more than 8,000 died of the disease. The five-year survival rate is about 60% for stage 3 melanoma and about 16% for stage 4, according to Moderna.

Moderna and other companies have been investigating the potential for a cancer vaccine using mRNA technology for years.

“When COVID occurred, they were able to take those learnings from the personalized cancer vaccine program and quickly adapt them to the urgent needs of the pandemic,” Brown said. “Now, the oncology program gets to benefit because… we sort of have a feel for what the safety profile is, the delivery systems, the manufacturer scaling, and all those learnings.”

Melanoma is very responsive to the immune system, which makes it a good place for vaccine makers to start when developing a new immunotherapy. If this technology continues to prove effective in future clinical trials, Brown said scientists could create immunotherapies to treat many other types of cancers.

Harnessing the Body for a Personalized Cancer Vaccine

Moderna’s phase 2b trial included 157 people with stage 3 or 4 melanoma and a high risk of cancer recurrence. About a third of the patients received Keytruda alone, while the others got a combination of Keytruda and the vaccine.

As with all human cells, cancer cells carry proteins that keep them from being attacked by their own immune system. Keytruda acts as an “immune checkpoint inhibitor,” blocking these proteins and giving the immune system leeway to attack cancer cells.

That’s where the vaccines come in. Just as the COVID-19 mRNA vaccines tell the immune system to recognize the virus’ spike protein, the cancer vaccines prime the immune system and Keytruda to wage a more targeted attack should the melanoma return.

Among the biggest challenges in creating a cancer vaccine is learning how to target the unique mutations in each person’s cancer, said Alexander Huang, MD, an assistant professor of medicine at the University of Pennsylvania Institute of Immunology.

“For COVID, it’s the same virus across much of the population. What we’ve realized is that in each cancer, even across the same cancer type—say, melanoma—each person’s cancer is unique to that patient. A lot of that comes from the person’s DNA and then the type of mutations they receive,” Huang said.

Before the trial, all of the patients in the Moderna study had surgery to remove their tumors. Moderna scientists then biopsied their melanoma and genetically tested it to understand which antigens—substances that trigger an immune response–are being expressed by that patient’s tumor. The team combined up to 34 antigens for each patient into a single mRNA vaccine.

It took about six weeks for Moderna to collect and sequence the patient’s tumor sample, manufacture their personalized vaccine, and have it ready for the patient to start treatment.

One group was given Keytruda alone for 18 treatment cycles, or about a year. The other group received Keytruda and nine total doses of the cancer vaccine called mRNA-4157.

The combination treatment reduced the risk of recurrence or death by 44%. The company has not yet shared more specific data on the patients’ immune response, like their T cell levels.

Compared to other treatment options, like chemotherapy, the vaccine side effects were relatively benign. Serious adverse events related to the treatment occurred in 14.4% of patients who received the combination, compared to 10% of those who got Keytruda alone.

The Moderna data is still in early days, but the results are promising so far, Huang said.

Huang said scientists have long seen promise with personalized cancer vaccines, but the clinical data has so far been inconsistent. These results are an indication that the treatment actually benefits patients.

Opening the Door for More Cancer Vaccines

In some cases, receiving medications like Keytruda early in a patient’s cancer progression could limit the effectiveness of other treatments later on, according to Brown. If cancer vaccines turn out to be safe and effective for the early stages of cancer, patients could use those immunotherapies, rather than Keytruda alone, and keep their treatment options open.

With more research, immunotherapies could even be used to shrink tumors in people with metastatic cancer, Huang said.

When a patient has metastatic cancer, which has spread from the primary location to another region of the body, they’re fighting against a large disease burden. In that state, nearly every advantage is on the tumor’s side. But by bolstering the immune system while the patient has no active tumors, the immune system gets the upper hand.

“This is where every advantage is on the immune system side, because you cut out all the tumor, you give them a big boost of their immune system, and then you have far more immune cells than tumor cells that you’re fighting—you’re just fighting the residual ones that are left after the surgery,” Huang said.

Scientists could use lessons learned from the Moderna vaccine to craft immunotherapies for people with metastatic cancer or those at an earlier stage of their disease.

“We’ve always wanted to do personalized medicine, precision medicine. And I think this is a beautiful example of the potential of it,” Huang said.

What This Means For You

If cancer vaccines continue to show success in clinical trials, they could become available to patients in the next couple years. As immunotherapy technology improves, cancer vaccines could be used to treat various tumor types and in earlier stages of disease.

1 Source
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  1. Centers for Disease Control and Prevention. Cancer statistics at a glance.

By Claire Bugos
Claire Bugos is a health and science reporter and writer and a 2020 National Association of Science Writers travel fellow.