“Game-changing” personalised cancer vaccine enters UK trials   

Melanoma or skin cancer

A clinical trial of a personalised mRNA cancer vaccine for melanoma patients has been launched in the UK. 

As reported by The Guardian, the global Phase III clinical trial is being led by University College London Hospitals NHS Foundation Trust (UCLH) and will include around 1,100 people, with the UK arm taking place across eight centres in the UK.  

It will trial the cancer vaccine known as mRNA-4157 (V940) which works by triggering the immune system to target neoantigens on tumours.   

mRNA-4157/V940 is a novel mRNA-based personalised cancer vaccine that encodes up to 34 patient-specific tumour neoantigens. In addition to encoding the target antigens, mRNA vaccines also provide adjuvant properties that amplify the immune response. 

The vaccines are personalised to each patient after a tumour sample is removed during surgery and then analysed using DNA sequencing. This means the vaccine can target the mutations unique to each patient’s tumour.  

A custom-built vaccine 

A Phase II trial of the vaccine in combination with the immunotherapy Keytruda (pembrolizumab) found that melanoma patients survived longer with this form of treatment compared to Keytruda alone.  

According to the results of the primary trial analysis, after 18 months, recurrence-free survival (RFS) was 78.6% in the combination arm and 62.2% in the Keytruda arm, corresponding to a 44% reduction in the risk of recurrence or death in patients who received both mRNA-4157/V940 and Keytruda. 

The vaccine has been labelled as a potential “gamechanger” in immunotherapy with the researchers’ ultimate aim of using it to help cure cancer.  

The national coordinating investigator of the trial, Dr Heather Shaw, said that the vaccine “is one of the most exciting things we’ve seen in a really long time. This is a really finely honed tool”.  

“This is very much an individualised therapy and it’s far cleverer in some senses than a vaccine,” said Shaw. “It is absolutely custom-built for the patient – you couldn’t give this to the next patient in the line because you wouldn’t expect it to work.” 

“They may have some shared new antigens, but they’re likely to have their own very individual new antigens that are important to their tumour and so, therefore, it is truly personalised,” Dr Shaw added. 

Melanoma affects around 16,700 people in the UK every year. Between 2017 and2019 there were 2,300 melanoma skin cancer deaths, accounting for around 1% of all cancer deaths. It is a largely preventable cancer and is treated using surgery, radiotherapy, chemotherapy and other cancer therapies. 

The vaccine is also being tested in other cancers including lung, bladder and kidney cancers.  

Earlier this year, another mRNA-based therapy started clinical trials investigating its potential in treating melanoma, lung cancer and other solid tumour cancers. 

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