November 14, 2024


Doctors have begun testing the world’s first personalized mRNA cancer vaccine for melanoma in hundreds of patients, as experts hailed its “game-changing” potential to permanently cure cancer.

Melanoma affects approximately 132,000 people a year worldwide and is the leading skin cancer killer. Currently, surgery is the main treatment although radiotherapy, medicine and chemotherapy are also sometimes used.

Now experts are testing new samples that are specially built for each patient and tell their body to look for cancer cells to prevent the disease from ever coming back.

A phase 2 trial found that the vaccines dramatically reduced the risk of the cancer returning in melanoma patients. Now a final phase 3 trial has been launched and is being led by University College London Hospitals NHS Foundation Trust (UCLH).

Dr Heather Shaw, the national coordinating investigator for the trial, said the jabs have the potential to cure people with melanoma and are being tested in other cancers including lung, bladder and kidney.

“It’s one of the most exciting things we’ve seen in a very long time,” Shaw said. “It is a very finely honed instrument. To be able to sit there and tell your patients 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 comes to them… The patients are really excited about them.”

The vaccine is an individualized neoantigen therapy. It is designed to activate the immune system so that it can fight back against a patient’s specific type of cancer and tumor.

Known as mRNA-4157 (V940), the vaccine targets tumor neoantigens, which are expressed by tumors in a specific patient. These are markers on the tumor that may be recognized by the immune system.

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

To personalize it, a tumor sample is removed during the patient’s surgery, followed by DNA sequencing and the use of artificial intelligence. The result is a customized anti-cancer shot that is specific to the patient’s tumor.

Dr Heather Shaw talks to Steve Young, one of the first patients on the UCLH trial. Photo: Yui Mok/PA

“It’s very much an individualized therapy and it’s much smarter than a vaccine in some ways,” Shaw said. “It was built absolutely specifically for the patient – ​​you couldn’t give it to the next patient in line because you wouldn’t expect it to work.

“They may have some shared new antigens, but they will likely have their own very individual new antigens that are important to their tumor and so it’s really personalized.”

The ultimate goal is to permanently cure patients of their cancer, Shaw said. “I think there is real hope that these will be the game changers in immunotherapy,” she said.

Phase 2 data found that people with severe, high-risk melanomas who had the shot alongside the immunotherapy Keytruda were almost half (49%) as likely to die or have their cancer come back after three years than those who only received Keytruda was given.

Patients received 1 mg of the mRNA vaccine every three weeks for a maximum of nine doses, and 200 mg of Keytruda every three weeks (maximum of 18 doses) for about a year.

The phase 3 global trial will now include a larger range of patients, and aims 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.

One of the first patients on the trial at UCLH is Steve Young, 52, from Stevenage in Hertfordshire. “I’m really, really excited,” he said. “This is my best chance to stop the cancer in its tracks.”



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