Melanoma: how the first mRNA vaccine against cancer works

A vaccine that helps the immune system recognize tumor cells, used together with an immunotherapy drug, reduced the recurrence of melanoma by 42% in patients who had already undergone surgery to remove this type of tumor.

The mRNA vaccine, developed by the pharmaceutical companies Merck and Moderna, uses technology similar to that of the vaccines that brought us out of the Covid pandemic to prevent the risk of melanoma recurrence – therefore, not to prevent the initial appearance of this tumor.

The very promising results of the phase 3 trial were anticipated last June, but were confirmed and explained in greater detail during the European Society for Medical Oncology (ESMO) congress held in Madrid on 24 October.

As explained above Naturethe combination of the vaccine and immunotherapy is designed for patients whose melanoma may return after surgery and who do not respond well to immunotherapy alone.

The treatment of melanoma has made great strides in recent years. Only 15 years ago, patients with advanced forms of melanoma had an estimated survival of a few months. Today, almost 55% are effectively treated with molecularly targeted therapy (target therapy: drugs that bind to molecular targets on tumor cells with a highly selective action), or with immunotherapy drugs, which reactivate the cells of the immune system so as to make them react against tumor cells.

The personalized vaccine, called intismeranis tailor-made based on the genetic profile of the patient’s tumor. The scientists sequenced the DNA of melanoma samples from patients who had already undergone melanoma removal surgery, to identify mutations present in the tumor cells.

These mutations give rise to proteins called neoantigens, which help distinguish cancer cells from healthy ones. The vaccine contains instructions to encode proteins with up to 34 of these mutations: it is as if the patient’s immune system was presented with a fingerprint of the proteins associated with that specific type of melanoma.

The vaccine induces the patient’s cells to produce proteins with these neoantigens, which like “flags” attract the attention of the immune system and tell it where to attack. Thanks to this training, the patient’s T cells refine their ability to recognize and attack tumor cells that present the same neoantigens.

The experimental vaccine is administered in combination with an immunotherapy drug, the pembrolizumabalready used against melanoma, which stimulates the immune system to attack tumor cells, induces them to self-destruct and hinders the formation of blood vessels that feed the tumor.

The phase 3 study involved 1137 patients from 157 centers, with forms of melanoma at risk of recurrence in sites distant from the original one, who received the personalized vaccine together with immunotherapy or immunotherapy alone plus a placebo, every 3 weeks for one year. Participants were monitored for about 25 months after treatment, and will remain monitored for a few years, to determine whether the vaccine improves overall survival as well as reducing the risk of recurrence.

Two years after starting therapy, 82% of participants who received the combination of drugs were alive and had not had their melanoma return, compared to 70% of patients who received the immunotherapy and placebo. The vaccine did not cause any major side effects.

Now the group of scientists who conducted the study, led by Georgina Long, oncologist at the Melanoma Institute Australia in Sydney, is carrying out statistical investigations to understand which patients can benefit most from the vaccine, which could be approved in Europe and the USA in 2027.

In fact, creating a personalized vaccine requires a lot of time (even just to obtain the appropriate sample of tumor cells) and involves very high costs: in January, a Reuters report estimated that around 200,000 dollars per patient are needed, a figure that is difficult for healthcare systems to sustain on a large scale.