mRNA cancer vaccine: success in melanoma patients

Moderna, the American developer of mRNA vaccines, announced the results of a phase 2b study (Keynote-942) on Tuesday afternoon. “The current results are very encouraging for the application field in cancer therapy. the mRNA-Technology has revolutionized the situation with Covid-19. Now, for the first time, we have been able to demonstrate the potential of the technique in treatment outcomes in a randomized clinical trial of melanoma. We are starting additional research into melanoma and other cancers. The goal is fully individualized cancer therapies,” said Stephane Bancel, CEO of the company.

Stage III or IV disease
The study, which was conducted in combination with Moderna and MSD, involved 157 melanoma patients. They had advanced stage III or IV disease and also had lymph node involvement without distant metastases. The tumor could be completely removed surgically. Nevertheless, the patients had a high risk of recurrence.

To prevent recurrence of the disease, the subjects received two different additional therapies: half received 200 milligrams of the anti-PD-1 immunotherapeutic drug pembrolizumab every three weeks and up to 18 times for about a year. This monoclonal antibody has been an immunotherapeutic agent for many years and has now been studied in some 1,700 studies. It is what is known as an immune checkpoint inhibitor.

The second half of the participating patients received pembrolizumab and additionally an individually manufactured according to the molecular characteristics of “their” melanoma mRNA– Moderna cancer vaccine (mRNA-4157/V940). This happened in nine partial vaccinations. mRNA-4157/V940 is a candidate cancer vaccine based on messenger ribonucleic acid (mRNA), encoding up to 34 so-called neoantigens from the individual tumor. This is intended to trigger an immune response against the melanoma’s typical mutated proteins. After the injection, the patient’s cells produce these proteins, they are presented to the immune system as “foreign” and must then be fought. Overall, the strategy is designed to complement and enhance immune checkpoint inhibitor therapy.

Greatly reduced risk of death
The results showed a very clear picture: Compared with pembrolizumab alone, the combination therapy reduced the frequency of recurrences with recurrence of the melanoma or deaths from the cancer from 14.4 percent to 10 percent. This meant a 40 percent reduction in the risk of recurrence and death.

Many studies with personalized cancer vaccines
Studies with personalized cancer vaccines have been ongoing worldwide for years. They are designed to activate the immune system in such a way that a patient can generate an individual anti-tumour response tailored to the signature of their tumor mutation. The resulting specific T-lymphocytes should then fight the malignant tissue. However, many experts believe that immunological therapies probably work best when combined with additional treatment modalities. That’s why MSD and Moderna decided to test cancer vaccines and immune checkpoint inhibitors.

The two American companies are with the mRNATumor vaccines are far from alone in this field. the mRNAtechnology was originally developed for hopeful cancer vaccines. This was also the case, for example, at BioNTech. However, with the emergence of SARS-CoV-2 and the Covid-19 pandemic, it was possible to use this process to develop and produce effective vaccines against a pathogen at an unprecedented speed. MSD and Moderna are developing the new cancer combination therapy in a joint venture. If diagnosed too late, melanoma is an extremely insidious cancer. The diagnosis is currently made in approximately 325,000 patients per year worldwide.