Personalised mRNA melanoma vaccine cuts cancer's return in first late-stage success

A personalised mRNA vaccine for melanoma has reduced the risk of the skin cancer returning in a phase III clinical trial, its developers Merck & Co (MSD) and Moderna announced — the first mRNA-based cancer treatment to show success in a late-stage trial (Nature; BBC News).

The trial enrolled around 1,100 patients with high-risk stage II–IV melanoma whose tumours had been surgically removed. Participants received either the vaccine, called intismeran, combined with the immunotherapy drug pembrolizumab (Keytruda), or pembrolizumab alone. The companies said those on the combined treatment survived longer without recurrence and had a reduced risk of the disease spreading to other organs; detailed data are due to be presented at a medical conference in October (BBC News; Nature).

To make each dose, scientists sequence a sample of a patient's tumour to identify mutations that produce abnormal proteins, or neoantigens, which flag cancer cells to the immune system. The mRNA vaccine is then built to match that individual's neoantigens, instructing the body to recognise and attack any remaining tumour cells. "We had never been able to train an individual patient's immune system against their own tumour before," said Adnan Khattak, a medical oncologist and trial investigator at Hollywood Private Hospital in Nedlands, Australia (Nature).

Experts hailed the result as proof of principle but urged caution because the interim findings have not yet been peer-reviewed. "It provides proof of principle that personalised cancer vaccines work," said Dr Lennard Lee, a consultant medical oncologist at the University of Oxford. Marco Gerlinger, a medical oncologist at St Bartholomew's Hospital in London, said the approach "can be designed against many different cancer types," while Seth Cheetham, an mRNA scientist at the University of Queensland, called it "incredibly exciting" as the first large-scale trial of a personalised mRNA cancer vaccine to release data (BBC News; Nature).

Significant hurdles remain before wider use: each vaccine can take several months to manufacture, and Khattak noted participants must be monitored for years to establish whether the treatment extends lifespan. Prof Peter Johnson, NHS England's national clinical director for cancer, said the NHS was preparing to bring this type of treatment to patients, and Cancer Research UK's Dr Talisia Quallo said the research "shows promise" but the data still need full review. Merck and Moderna are testing similar personalised vaccines for lung, bladder and kidney cancers (BBC News; Nature).

**Sources:** Nature, BBC