In April 2024 we learnt of a trial of a personalised mRNA vaccine against the most dangerous form of skin cancer, melanoma. Recruitment for the University College London Hospital trial began in October 2023, and is expected to involve more than 60-70 patients at 8 centres. The treatment is a combination approach using mRNA-4157 (V4940) and Keytruda. Principal Investigator, Dr Heather Shaw, hopes that this therapy could be a “gamechanger”.
Melanoma
Melanoma skin cancer is caused by abnormal cell growth and division in an “uncontrolled” way, starting in melanocytes, found in the epidermis. Melanocytes provide melanin, which gives the skin colour and protects the body from ultraviolet light from the sun. In people with white skin, melanoma is “more common on skin that has been exposed to the sun” but can start anywhere. In people with brown or black skin, melanocytes are “more active”.
Although melanoma is often associated with sun exposure, it can also “rarely” develop in areas that have not been exposed to the sun, which is called acral melanoma. An estimated 16,700 people are diagnosed with melanoma skin cancer in the UK each year, and this number has been increasing over recent decades. Melanoma skin cancer is the 5th most common cancer in the UK.
A possible solution
The treatment, developed by Moderna and MSD, is being investigated in several countries. The personalised vaccine encodes up to 34 neoantigens determined from analysis of the tumour removed from the patient in surgery. Dr Shaw explains that this is “one of the most exciting things we’ve seen in a really long time”.
“It is absolutely custom built for the patients – you couldn’t give this to the next patient in the line…it’s truly personalised.”
Dr Shaw describes the vaccine as a “finely honed tool”, which she is excited to offer to patients.
“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 McDonalds – it’s that level of cordon bleu that’s coming to them.”
Fighting an unseen enemy
One of the first patients in the trial is Steve Young, who had surgery to remove a melanoma growth on his scalp last year. He told BBC Radio 4’s Today Programme that the opportunity to participate in the trial “gave me a chance to feel like I was actually doing something to fight a potential unseen enemy”. While scans suggest that Mr Young is “radiologically clear”, there is a chance that there are “cancer cells floating around undetected”.
“Rather than just sit there and wait and hope it was never going to come back, I actually had this chance to get involved in putting on some boxing gloves and squaring up to it.”
Modern developments
Professor Lawrence Young from the University of Warwick commented that “this is one of the most exciting developments in modern cancer therapy”, with the approach having “already shown great promise” in earlier trials. The new study is part of a global trial to assess “more fully” the efficacy of the combination immunotherapy.
“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.”
Professor Young is hopeful that the approach “could be extended to other cancers” such as “those of the lung and colon”.
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