The New Wave of Personalized mRNA Cancer Vaccines

For years, the idea of a vaccine designed specifically for a person's cancer sounded more like science fiction than medicine. Vaccines are traditionally associated with infections, whether bacterial or viral. Cancer is different, and the path toward prevention has always been viewed as unique. Primarily because cancer is a collection of diseases in which a person's own cells acquire mutations and begin growing uncontrollably.

Moderna and Merck may be changing that. According to a recent announcement, Merck and Moderna have seen promising results from a large late-stage trial of an experimental personalized mRNA cancer vaccine designed to help prevent melanoma from returning after surgery. The treatment, known as intismeran autogene, was given alongside Merck's immunotherapy Keytruda. While the treatment is still experimental and has not been approved by the FDA, the announcement has energized the world of cancer treatment and prevention.

Cancer Vaccines Aren't Really Like Traditional Vaccines

The phrase “cancer vaccines” is a bit misleading. Traditional vaccines work by preventing a person from catching a disease, or by reducing the likelihood of them catching a specific strain of an illness. Cancer vaccine research has long been based on the idea of teaching the immune system to identify and attack cancer cells that are already present, as well as those that can come back after treatment.

That distinction is particularly important for personalized mRNA cancer vaccines. The goal isn't necessarily to create one universal vaccine for everyone with melanoma, pancreatic cancer, or another disease. Instead, researchers aim to create a treatment based on the specific mutations found in an individual patient's tumor.

The Tumor Helps Design the Treatment

This type of personalized cancer treatment begins by taking a sample of the patient’s tumor. Scientists then analyze the characteristics of the tumor and look for mutations that distinguish cancer cells from the healthy cells that are present. These mutations can produce abnormal proteins or fragments called neoantigens.

The immune system may be capable of recognizing these unusual features, but the challenge is in finding which ones are most useful. When that determination is made, researchers can design an mRNA vaccine containing instructions intended to teach the immune system to recognize those tumor-specific targets. According to researchers involved with the recent study, the idea is to provide the immune system with what amounts to a “list of wanted posters.”

mRNA Makes the Concept More Flexible

The technology behind this cancer vaccine research became widely known during the COVID-19 pandemic. mRNA, or messenger RNA, carries instructions that cells can use to produce proteins. COVID-19 vaccines showed that this technology could be produced at an enormous scale. Since the vaccine delivers information to multiple targets, researchers are increasingly interested in mRNA.

With this information in mind, scientists from Moderna and Merck believe that a cancer vaccine can be designed around the mutations identified in one person's tumor rather than requiring researchers to create an entirely different technological platform for every cancer. Researchers have described mRNA as a potentially useful platform for generating patient-specific neoantigen vaccines, although significant challenges remain.

The Latest Melanoma Results Are Important

The latest research published by Moderna and Merck involved 1,137 patients whose melanoma had been surgically removed, but the patients remained at “high risk” for a recurrence. Patients received either the personalized vaccine combined with Keytruda or Keytruda alone. According to scientists involved with the project, the combination produced statistically significant and clinically meaningful improvements in both recurrence-free survival and distant metastasis-free survival.

Patients who received the combination of Keytruda and a personalized vaccine went longer without their cancer returning than patients who received Keytruda alone. The size and scope of the experiment make the findings even more interesting. It was a large Phase 3 clinical trial, the stage of research generally used to provide the evidence needed for regulatory review.

The Idea Isn't Limited to Melanoma

While the recent study focused on melanoma, researchers have no plans of stopping there. Moderna and Merck are expanding their investigations into additional cancers, including non-small cell lung cancer, bladder cancer, kidney cancer, pancreatic cancer, and stomach cancer. Meanwhile, other companies are actively pursuing similar strategies.

Ultimately, it remains to be seen how the research gathered in the melanoma study will be applied to other types of cancer. A type of treatment that attacks one type of cancer may not be as powerful against other types. However, the findings are considered encouraging by researchers affiliated with the study and experts who have been monitoring the results.

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