Lennard Lee
What is this personalised cancer vaccine and how does it work?
“Personalised cancer vaccines are a fundamentally different way of thinking about cancer treatment. Rather than giving every patient the same medicine, a treatment is designed specifically for the individual patient and the unique genetic fingerprint of their cancer.
“A sample of the patient’s tumour is analysed to identify mutations that distinguish the cancer cells from healthy cells. These mutations can generate abnormal proteins, known as neoantigens, which can potentially be recognised by the immune system. The vaccine uses mRNA to provide instructions corresponding to selected neoantigens, with the aim of training the patient’s immune system, particularly its T cells, to recognise and attack cancer cells carrying them.
“In this trial, each personalised treatment encodes up to 34 neoantigens and is given alongside pembrolizumab, an established immunotherapy. In simple terms, one treatment helps show the immune system what to look for, while the other helps release the brakes on the immune response.
What can we know from these results, and what details are still to come?
“What we know today is important. This was a large Phase III randomised trial involving 1,137 patients with surgically removed, high-risk melanoma, and the trial met its primary endpoint.
“According to the topline announcement, patients receiving the personalised mRNA cancer vaccine alongside pembrolizumab had a statistically significant and clinically meaningful improvement in recurrence-free survival compared with pembrolizumab alone. The study also met the important secondary endpoint of distant metastasis-free survival.
“That is very encouraging. We should now look forward to seeing the complete data. We do not yet have the magnitude of the Phase III benefit, the detailed subgroup analyses, quality-of-life data or mature overall-survival results. Those details will allow the scientific and clinical community to understand precisely how large the benefit is, which patients benefit most, and ultimately where this treatment might sit within routine melanoma care.”
How significant are these findings?
“These findings are significant. This is the first positive Phase III trial of an individualised neoantigen therapy and an mRNA-based cancer treatment. That makes this an important moment for a field that scientists have been working towards for many years. Within 6 years of the pandemic, we have mRNA vaccines to treat cancer.
“There is also a wider story here about what happened after the pandemic. In 2020, enormous global investment accelerated mRNA technology, vaccine science and manufacturing, and it started in the United Kingdom. The question afterwards was whether that capability could be redirected towards other major diseases.
“In 2022, the UK made an early strategic decision to pursue that opportunity in cancer, launching a national cancer vaccine advance to accelerate clinical trials of mRNA cancer vaccines. It forms part of our AI For Science Plan, our 10-year cancer plan, and our modern industrial strategy. Since then, the UK has developed into one of the world’s leading environments for cancer vaccine trials. Nearly 50 cancer centres have contributed to this national effort, including through programmes such as the NHS Cancer Vaccine Launch Pad and Vaccine Innovation Pathway, alongside expert contributions to the MHRA. We have even made a major push into AI, using our AI Supercomputer to significantly improve design of these vaccines.”