Personalised mRNA-based vaccine trial shows encouraging results for melanoma

Phase 3 trial results for an experimental vaccine based on mRNA technology indicate positive initial outcomes for treating high-risk melanoma patients, potentially representing the arrival of a unique form of cancer therapy.

The vaccine, developed by Merck and Moderna and known as intismeran, was trialled in over 1100 participants with completely resected melanoma. These patients had had their cancerous lesions removed surgically, but they were still at risk of seeing their cancer come back due to cancerous cells potentially persisting in their body. In combination with an immunotherapy called pembrolizumab, intismeran reached its primary endpoint of recurrence-free survival, according to an announcement made by the two companies.

'Today's results represent a landmark moment for adjuvant melanoma treatment', said Professor Georgina Long, medical director of Melanoma Institute Australia and the principal investigator of the study. 'Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.'

The results are yet to be published, as the trial is continuing in order to evaluate other secondary outcomes such as overall survival. However, these results build on previous positive Phase 2 results, and the researchers intend to present their findings at an upcoming medical conference in October.

Intismeran, an mRNA-based vaccine based on the same technology used to develop COVID vaccines, induces the immune system to kill cancer cells by targeting proteins on their surface called 'antigens'. The immune system recognises antigens typically carried by infected or 'foreign' cells, which can then be destroyed. By providing a small amount of the mRNA used to create specific antigens, the vaccine helps the immune system get trained to target any cells presenting such proteins.

However, since cancer cells are derived from healthy tissue, the antigens they present are not highlighted as foreign, and the cancer can evade the immune system. Additionally, every tumour is genetically unique and produces its own antigens, meaning that a universal vaccine targeting a specific antigen cannot be developed.

The researchers overcame these limitations by examining the resected tumours of each patient and identifying the unique mutations that create new antigens in the cancerous cells of a given individual. Bespoke, patient-specific vaccines could then be developed to target cells displaying these specific 'neoantigens'.

'These Phase 3 findings represent a pivotal moment for the field of cancer research', said Stéphane Bancel, CEO of Moderna. He added: 'For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality.'

Melanoma has long been at the forefront of immunotherapy research, since skin cancers accrue lots of mutations which result in more neoantigens being created. However, Moderna and Merck are also trialling mRNA vaccines in other 'immune-hot' cancers such as lung, bladder, and kidney cancers. Additionally, future work may focus on highlighting biomarkers, such as high numbers of mutations, which could identify more patients who could benefit the most from such treatments.

Dr Lennard Lee, an associate professor at Oxford University and a consultant medical oncologist, commented to the BBC: 'This is certainly good news for patients with melanoma, but the study has much wider implications. It provides proof of principle that personalised cancer vaccines work.'