Vaccine raises hope in fight against skin cancer

After playing tennis, he suddenly felt pain in his left arm. "I went to the clinic and was diagnosed with melanoma," says a patient from Hamburg. He knows full well that even if the tumor is removed, it can return or metastasize.

This risk is very high in melanoma, also called black skin cancer. The patient therefore decided to participate in a study investigating whether an mRNA vaccine against melanoma could reduce the risk of recurrence. The aim of the vaccination is to train the immune system to recognize and destroy tumor cells.

Effect visible even after five years

“We know that in practically every patient with a healthy immune system who develops melanoma, an immune attack is already underway – the defense system is already trying to attack and destroy these cells,” explains Christopher Gebhart from the Department of Dermatology at the University Hospital Hamburg-Eppendorf (UKE). Gebhart is leading the Hamburg part of the so-called phase 3 study, which is currently underway. He emphasizes that these immune reactions now need to be further strengthened.

The first, smaller phase 2 study, which involved 157 patients, showed after just two years that the combination of immunotherapy and mRNA vaccine significantly more effectively reduces the risk of disease recurrence than immunotherapy alone.

In this study, patients with black skin cancer first had their melanoma removed. They all then received drugs via infusion, or immunotherapy. Two-thirds of the patients also received an mRNA vaccine, which was tailored to their specific tumor. Now, five years later, new results have been published showing that the risk of recurrence remains reduced in the long term.

Vaccine combined with immunotherapy

These mRNA studies connect two concepts that rely on immunity.

During the infusion, patients are given so-called checkpoint inhibitors that activate the defense system.

"We know that these drugs are effective, but probably only in a subset of patients, about half. The other half seem to be resistant to this type of immunotherapy," says Gebhart.

The role of the mRNA vaccine is to complement these inhibitors by “showing” immune cells exactly where the cancer cells are.

Individual mRNA vaccine for each patient

The treatment lasts a year. "I just received my fifth infusion and my third vaccine. I felt absolutely nothing from the vaccines themselves," says a patient participating in the current study. "I only felt a slight pain at the injection site, without any other typical reactions."

The mRNA vaccine is manufactured individually for each patient, based on their tumor. A tissue sample is sent to vaccine manufacturer Moderna, where the genetic code of the tumor cells is deciphered and compared to the body's healthy cells.

Dermatologist Gebhart explains that this is the secret of the programmers and manufacturers. They select from the list of genetic changes those that contain information about the protein structures that the immune system recognizes best – so-called neoantigens. In this case, between 20 and 34 different neoantigens are selected and then administered to the patient.

A greater number of patients remained healthy

Now, five years later, the health status of the participants from phase 2 of this study has been re-checked to determine who had cancer and who had not. Analysis of the data showed that the effect lasts long if the immune system successfully learns how to fight the tumor.

“We see that this is not a temporary effect,” says Ralf Gützmer, director of the University Clinic for Skin Diseases in Minden and chairman of the Working Group for Dermatological Oncology. Fewer relapses and distant metastases were recorded. “This means that more patients remain healthy, although without this therapy they would have a high risk of the disease returning.”

Gucmer emphasizes that this is the first data proving that the effect lasts even after five years.

The knowledge that the effect is not weakening has reinforced the high expectations that doctors have for the mRNA vaccine. Gebhart is also optimistic:

"MRNA vaccine technology could revolutionize the treatment of melanoma and allow us to cure significantly more patients than before."

The vaccine has not yet been approved and will be expensive.

However, the mRNA vaccine against melanoma has not yet been approved for official use. A prerequisite for approval is that a large phase 3 study, involving more than 1.000 patients, confirms these positive results. The outcome of that study is expected in the fall at the earliest.

Even if the vaccine is approved, the problem of its price remains.

"It certainly won't be a cheap therapy," warns Gebhart.

A year of inhibitor therapy, as well as the individual production, preparation and administration of the mRNA vaccination itself, are extremely expensive. This expert estimates that the price could be more than 100.000 euros per patient per year. So far, very few services in medicine have been recorded that are so expensive.