British patients test world’s first personalised mRNA jab for melanoma

The world’s first personalised mRNA cancer jab for melanoma – which also has the potential to stop lung, bladder and kidney cancer – is being tested in British patients.

The “gamechanger” jab, which offers hope of a cure, is custom-built for each person in just a few weeks.

It works by telling the body to hunt down cancer cells and prevent the deadly disease from coming back.

A stage 2 trial of the jab, involving pharma firms Moderna and MSD, found it dramatically reduced the risk of the cancer returning in melanoma patients.

Now a final phase 3 trial has been launched, led by University College London Hospitals NHS Foundation Trust (UCLH).

Dr Heather Shaw, national co-ordinating investigator for the trial, said the jab had the potential to cure people with melanoma and is being tested in other cancers.

Sharing the trial details exclusively with the PA news agency, she said: “This is one of the most exciting things we’ve seen in a really long time.

“This is a really finely honed tool. To be able to sit there and say to your patients that you’re offering them something that’s effectively like the Fat Duck at Bray versus McDonald’s – it’s that level of cordon bleu that’s coming to them.

“These things are hugely technical and finely generated for the patient. The patients are really excited about them.”

The new jab is an individualised neoantigen therapy (INT) and is sometimes referred to as a cancer vaccine.

It is designed to trigger the immune system so it can fight back against the patient’s specific type of cancer and tumour.

Known as mRNA-4157 (V940), the jab is created to target tumour neoantigens, which are expressed by tumours in a particular patient.

These are markers on the tumour which can potentially be recognised by the immune system.

The jab carries coding for up to 34 neoantigens and activates an anti-tumour immune response based on the unique mutations in a patient’s cancer.

In order to create the jab, a sample of tumour is removed during the patient’s surgery, followed by DNA sequencing and the use of artificial intelligence.

The result is a personalised anti-cancer jab which is specific to the patient’s tumour.

Dr Shaw said: “This is very much an individualised therapy and it’s far cleverer in some senses than a vaccine.

“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.”

The ultimate aim is to cure patients of their cancer, Dr Shaw said.

“Absolutely, that’s the drive. With (this) therapy, what you’re doing is dealing with the theoretical risk that the cancer could recur.

“So there’s nothing to see on scans, but if there are some cells that have escaped that are below the detection of imaging… what we’re trying to do is, on a patient-by-patient basis, give treatment to eradicate any of those rogue cells that might be sitting about.

“What we’re trying to do is to push more patients into that recurrence-free survival bucket, which should translate into overall survival benefit and a non-recurrence of those patients over time, which equals cure.”

Phase 2 data, published in December, found that people with serious high-risk melanomas who received the jab alongside MSD’s immunotherapy Keytruda were almost half (49%) as likely to die or have their cancer come back after three years than those who were given only Keytruda.

Patients received one milligram of the mRNA vaccine every three weeks for a maximum of nine doses, and 200 milligrams of Keytruda every three weeks (maximum 18 doses) for about a year.

The phase 3 global trial will now include a wider range of patients, and hopes to recruit around 1,100 people.

The UK arm aims to recruit at least 60 to 70 patients across eight centres, including in London, Manchester, Edinburgh and Leeds.

The therapy combination is also being trialled in lung, bladder and kidney cancer.

One of the first patients on the trial at UCLH is Steve Young, 52, from Stevenage.

His “bump on the head” – which he thinks he had for around a decade – turned out to be melanoma.

He told PA it was a “massive shock” to be diagnosed.

“I literally spent two weeks just thinking ‘this is it’,” he said.

“My dad died of emphysema when he was 57 and I actually thought ‘I’m going to die younger than my dad’.”

Mr Young said when he was told about the trial at UCLH it “really triggered my geek radar”.

He added: “It really piqued my interest. As soon as they mentioned this mRNA technology that was being used to potentially fight cancer, I was just like, ‘it sounds fascinating’ and I still feel the same. I’m really, really excited.

“This is my best chance at stopping the cancer in its tracks.”

Dr Shaw said: “I think there is a real hope that these will be the gamechangers in immunotherapy.

“We’ve looked for a long time for something that would be additive to the immunotherapies that we already have – that we know can be life-changing for patients – but with something that’s got a really acceptable side-effect profile.

“And these therapies look as if they may offer that promise.”

Dr Shaw said side effects include tiredness and a sore arm where the jab was given.

“So it appears to be relatively tolerable and actually no worse than having a flu vaccine or a Covid jab for the majority of patients,” she said.

Professor Lawrence Young, from the University of Warwick, said: “This is one of the most exciting developments in modern cancer therapy.

“Combining a personalised cancer vaccine to boost a specific immune response to the patient’s tumour along with using an antibody to release the brake on the body’s immune response has already shown great promise in patients whose original skin cancer (melanoma) has been removed.

“Interest in cancer vaccines has been reignited in recent years by a deeper understanding of how the body controls immune responses and by the advent of mRNA vaccines which makes developing a vaccine based on the immune profile of a patient’s own tumour much more straightforward.

“The hope is that this approach could be extended to other cancers such those of the lung and colon.”

Vassiliki Karantza, associate vice president of MSD Research Laboratories, said: “At MSD, we are committed to driving research forward for innovative modalities in earlier stages of cancer, where we can have the most meaningful impact on patients.

“This trial demonstrates our continued efforts to advance novel treatment options for patients with melanoma and we look forward to the expansion of our comprehensive clinical development programme into additional tumour types.”