How does Moderna’s new melanoma vaccine work – and could it treat other cancers?

Moderna and Merck have announced that a personalized mRNA cancer vaccine significantly reduces the recurrence of melanoma following surgical removal. This marks the first time an mRNA-based cancer treatment has demonstrated effectiveness in a phase III clinical trial, offering hope for future regulatory approvals and broader applications in personalized medicine. The vaccine, named intismeran, employs the same messenger RNA (mRNA) technology used in the development of successful COVID-19 vaccines. Unlike traditional preventive vaccines, intismeran does not aim to stop cancer from developing initially but instead focuses on preventing its return after treatment. The phase III trial involved approximately 1,100 patients with advanced melanoma whose tumors had been surgically removed. Participants were divided into two groups: one receiving the vaccine alongside pembrolizumab, an existing immunotherapy drug, and another receiving pembrolizumab alone. Those treated with the combination showed a longer period without cancer recurrence compared to those given pembrolizumab alone. Developed by Merck in Rahway, New Jersey, and Moderna based in Cambridge, Massachusetts, the vaccine is tailored to each patient's specific tumor profile. A sample of the tumor is analyzed to identify genetic mutations that lead to the production of abnormal proteins known as neoantigens. These proteins serve as markers for the immune system to target. The mRNA vaccine instructs the body to produce these neoantigens, thereby training the immune system to recognize and attack cancer cells. “This is the first really large-scale trial to release data for a personalized mRNA cancer vaccine,” said Seth Cheetham, an mRNA scientist at the University of Queensland in Brisbane, Australia. He emphasized the significance of the findings, noting that they bring the vaccine closer to regulatory approval and could enhance the credibility of personalized cancer treatments. Marco Gerlinge, a medical oncologist at St Bartholomew’s Hospital in London, highlighted the importance of the study, stating it provides evidence that personalized cancer vaccines can be effective across various cancer types. Gerlinge is also a principal investigator on a similar trial involving a cancer vaccine being developed by BioNTech in Mainz, Germany. Sam Barrell, CEO of the medical research charity LifeArc in London, noted that the study could influence other areas of medicine beyond oncology. She suggested that the approach could benefit patients with rare diseases characterized by unique genetic mutations, promoting more tailored treatment strategies. Creating intismeran involves sequencing a patient's tumor to identify specific mutations. Each vaccine is then custom-made based on the identified neoantigens. According to Adnan Khattak, a medical oncologist and investigator in the trial at Hollywood Private Hospital in Nedlands, Australia, this process allows the immune system to be trained against the individual's tumor, a feat previously unachieved. Unlike conventional personalized cancer treatments that focus on targeting specific genetic abnormalities such as the BRAF mutation found in about half of melanomas, this study involved creating a novel drug for each participant. Cheetham explained that while the current results indicate a reduction in recurrence rates, further monitoring over many years is necessary to assess whether the treatment prolongs survival. Despite the promising outcomes, challenges remain in scaling up the production of such vaccines. Cheetham pointed out that the personalized aspect poses the greatest obstacle for widespread use. The process of creating a vaccine for each patient can take several months, and some individuals with advanced cancer may not live long enough to benefit from the treatment. Moderna utilizes artificial intelligence to identify which neoantigens are most likely to provoke a robust immune response. However, the complexity of manufacturing these highly customized vaccines presents logistical hurdles that must be addressed before they can become widely available. The companies involved plan to present more detailed data at an upcoming medical conference, providing further insights into the efficacy and potential applications of intismeran. As researchers continue to refine the technology, the path toward broader implementation of personalized cancer vaccines remains both challenging and promising.