The randomized phase 2b trial included men and women who had surgery to remove melanoma from lymph nodes or other organs and were at high risk of the disease coming back in sites distant from the original cancer.

Among the 107 study subjects who were injected with both the experimental vaccine, called mRNA-4157/V940, and the drug pembrolizumab, cancer recurred in 24 subjects (22.4%) within two years of follow-up, compared with 20 of 50 (40%) who received only pembrolizumab.

“Our phase 2b study shows that a neoantigen mRNA vaccine, when used in combination with pembrolizumab, resulted in a prolonged time without recurrence or death compared to pembrolizumab alone,” said study principal investigator Jeffrey Weber, deputy director. from the Perlmutter Cancer Center.

Results of the phase 2b trial were presented at the annual meeting of the American Association for Cancer Research in Orlando, Florida.

While phase 3 randomized trials test whether a treatment is superior to current standard therapies, phase 2 trials provide preliminary reassurance that one treatment is probably better than another, and lead to larger studies to confirm those results. Phase 3 trials of the mRNA-4157/V940 vaccine combination with pembrolizumab versus pembrolizumab alone are already planned at NYU Langone and other medical centers around the world, said Weber, the Laura and Isaac Perlmutter Professor of Oncology at the Department of of Medicine from NYU Grossman School of Medicine.

So far, the study results have led the US Food and Drug Administration (FDA) to grant Breakthrough Therapy Designation in February to mRNA-4157/V940 in combination with pembrolizumab, a designation designed to expedite reviews. government of test results.

The current results highlight the role of T cells in the immune system, capable of attacking both viruses and cancers. To preserve normal cells, this system uses “checkpoint” molecules on the surface of T cells to “turn off” their attack on viruses when they clear the infection. The body may recognize tumors as abnormal, but cancer cells hijack checkpoints to turn off, evade, and avoid immune responses. Immunotherapies like pembrolizumab try to block checkpoints, making cancer cells again more “visible” and vulnerable to immune cells.

Immunotherapies have become the mainstay of melanoma treatment, although they do not work in all patients because melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy. For this reason, researchers have studied the possibility of adding vaccines. Although most of the vaccines used today are designed to prevent infection, they can also be adapted to target proteins implicated in cancer.

Like the Covid-19 vaccine, mRNA-4157/V940 is based on messenger RNA, a chemical cousin of DNA that provides cells with instructions for making proteins. Cancer mRNA vaccines are designed to teach the body’s immune system to recognize cancer cells as different from normal cells. In designing a vaccine against melanoma, researchers tried to trigger an immune response against specific abnormal proteins, called ‘neoantigens’, made by cancer cells.

Since all of the study volunteers had their tumors removed, the researchers were able to analyze their cells for neoantigens specific to each melanoma and create a “personalized” vaccine for each patient. As a result, T cells specific for the neoantigen proteins encoded by the mRNA were produced. Those T cells could then attack any melanoma cells that tried to grow or spread.

Scientists involved in the study say the personalized mRNA-4157/V940 vaccine took six to eight weeks to develop for each patient and could recognize up to 34 neoantigens.