# This vaccine reduces risk of melanoma coming back. Can it work for other cancers? > Source: > Published: 2026-08-31 18:30:19+00:00 **Getting your** [Trinity Audio](//trinityaudio.ai)player ready...Intismeran Autogene, a vaccine that treats melanoma, a deadly type of skin cancer, has made headlines worldwide. Recently reported [results](https://www.merck.com/news/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-autogene-plus-keytruda-met-endpoints-of-recurrence-free-survival-rfs-and-distant-metastasis-free-survival-dmfs-in-patient/) indicate that the personalized medication, taken in combination with the immunotherapy Keytruda, met its main goal, reducing the chances of the cancer coming back within five years of the initial treatment by 49%. Jointly released by pharmaceutical giants Moderna and Merck, the medication uses mRNA, the same protein-encoding strategy used to make the first successful COVID-19 vaccines, to train immune cells to recognize and eliminate melanoma based on a computer prediction of the likely surface markers it carries. The first-ever phase three trial of a mRNA cancer vaccine is a major milestone in a strategy that has grown for more than a decade, with top research institutes across the globe proving in small clinical trials that they can create cancer vaccines capable of using the same system that detects viruses and bacteria to eliminate a range of malignancies, including melanoma, which is expected to kill more than 8,500 Americans this year. One such pioneer is translational immunologist Stephen Schoenberger at the La Jolla Institute for Immunology. Schoenberger worked with clinicians at UC San Diego in 2018 to create the first such vaccine ever administered by Moores Cancer Center. The LJI team’s approach was functional. Rather than using sophisticated computer algorithms alone to predict which markers on cancer cells — called “neoantigens”— could effectively be targeted, Schoenberger used tissue samples collected from each patient to determine which markers the immune system had already identified. They were astounded to learn that immune systems had already successfully primed T-cells, those immune system assassins that hunt down and destroy specific threats, to go after many different cancers. “We’ve detected pre-existing T-cells in more than 25 kinds of cancer, including types with very low levels of mutation, including sarcomas and brain cancers,” Schoenberger said. “Across the board, every kind of cancer that we’ve looked at, patients have developed pre-existing T-cells matched to their tumors.” But it is not enough to program T-cells with the neoantigens on cancer cells. Generally, these hunters do not start attacking cells unless there is a reason to do so, such as inflammation, a key marker of infection. Cancer vaccines require additional drugs called adjuvants in order to activate and start eliminating cancer cells. And many types of cancer, melanoma especially, produce abundant “checkpoint’ proteins on their surfaces capable of turning off T-cells even if they are perfectly primed to seek and destroy cells with distinguishing neoantigen markers. Moderna and Merck use pembrolizumab, a checkpoint inhibitor marketed as Keytruda, to address this evasive tactic. In 2024, after publishing his findings, Schoenberger predicted that a sea change in cancer therapy was likely in the coming decade. Three years later, it would appear that the new trial from Moderna and Merck, along with still-advancing work from a host of other research teams and LJI and across the globe, is delivering on that prediction. We asked Schoenberger for his opinions on what Intismeran Autogene means in the broader context of cancer immunotherapy. What follows is a condensed synopsis of his responses. Q: Generally, vaccines prevent infection, but cancer vaccines treat a condition that already exists in the body. Why are these medicines called vaccines if they’re not preventing an infection? A: The purpose of vaccination is to introduce an antigen, which is a unique marker that can distinguish normal cells from infected ones, to a patient’s immune system so that an immune response will be produced if that specific microbe is encountered. Cancer cells also have antigens, and if the immune system is primed to recognize them, it will act, even though cancer is something that already exists in the body. But the antigens that cancerous cells express differ significantly from patient to patient. They are not relatively consistent like the spike protein on the virus that causes COVID-19. So we must design a different cancer vaccine for each patient. Q: Intismeran Autogene uses messenger ribonucleic acid, mRNA, to create the molecule that attempts to program immune cells for 34 predicted neoantigens expressed on cancer cells. This is a different approach from the one that early cancer vaccines took. What do we know about why this mRNA approach appears to be effective, and what remains to be explained? A: mRNA vaccines, as we learned with COVID, are amenable to quick and industrialized manufacturing and to quick sequence changes, which you need to produce distinct versions for each individual. But the approach does work differently than other cancer vaccines have. Instead of creating a single molecule that targets a single neoantigen, the mRNA vaccine from Moderna and Merck makes a large molecule with 34 different neoantigens that must be processed by the cell in order to be presented to the immune system. So far, we have not seen the data that proves this approach actually primes the immune system in the same way that we have proven occurs with other cancer vaccines. Q: Obviously, something is occurring with the administration of this drug in nearly 1,000 patients, delivering phase three clinical trial results that have impressed the industry. What could be occurring to produce these results if not direct immune system programming to go after the unique features of cancer cells? A: This vaccine does not just contain mRNA but also a lipid envelope that has its own inflammatory potential. All of the patients also got Keytruda. We know that mRNA can trigger toll-like receptors that can turn on an inflammatory response in cells that can improve the effectiveness of checkpoint blockade drugs. There was a paper in Nature, which has stimulated a lot of debate in the field, showing that patients who received an mRNA COVID vaccine within 100 days of starting checkpoint blockade therapy had a more profound response in terms of tumor control and progression-free survival. Without the immune monitoring data proving that they’ve actually primed neoantigen-specific T-cells in their patients, it can’t be ruled out that this might be playing a role. Q: Moderna tested its mRNA cancer vaccine in patients with melanoma who had their tumors removed. The drug showed promising results in reducing recurrence, which is the cancer coming back. Is there reason to believe that this vaccine could be effective for patients with tumors that remain in place, especially in those whose melanoma has spread? A: The results so far in using therapeutic, personalized vaccines in the metastatic setting are rather poor. BioNTech’s neoantigen mRNA lipid nanoparticle vaccine phase 2 trial in the metastatic setting in melanoma failed to achieve its primary endpoints in melanoma. So I think there’s something special about using a vaccine that can hunt down the micrometastases that would otherwise lead to recurrence. Q: The vaccine that you produced was shown to be effective in several types of cancers, including some that are not as highly mutated as melanoma. A higher level of mutation, we know, makes it easier to find targetable neoantigens. Do you think that mRNA cancer vaccines could work against other types of cancer with neoantigens? A: If they are able to show that the multiple-antigen encoding approach can prime the immune system, and the T-cells that seek out and destroy cancer cells, then absolutely, it could work with cancers other than melanoma. Q: Overall, how important would you say these phase three clinical trial results are in the quest to make cancer vaccines the standard of care? A: I think this is a critical and necessary step in demonstrating that patients can be effectively vaccinated to prevent cancer recurrence. This is going to create new hope for the 1.7 million new cancer diagnoses that occur annually in this country, and it is going to lead to similar approaches or similar or aligned approaches being tried across a wide variety of cancer types. I fully expect to see cancer vaccines becoming frontline therapy to prevent cancer recurrence.