Can mRNA vaccines be a treatment for cancer?

One of the main revolutions in cancer treatment has been establishing personalised therapeutic decisions, taking into account the molecular features of each tumour. Cancer is a heterogeneous disease, with many variations between different tumours and also within the same type of tumour. This can make treatment difficult, which is why research projects and new therapeutic options are needed. 

In early April, the chief medical officer at the biotech company, Moderna, Dr Paul Burton, stated he hoped to offer new cancer vaccines by 2030. This led to certain expectations both in the healthcare field and in society. This statement followed on from data presented by Dr Jeffrey S. Weber from the KEYNOTE-942 study at the last meeting of the American Association for Cancer Research, held in Orlando. This was the first randomised study with pembrolizumab (anti-PD1) +/- mRNA-4157. This is a messenger RNA (mRNA) vaccine used as treatment in addition to surgery in high-risk melanoma.

These vaccines use mRNA, a type of genetic material that, in this case, carries information to manufacture tumour-specific molecules, called neoantigens. Their production is complex; as samples of the tumour and blood are needed to be sequenced and compared using bioinformatics analysis, before finally selecting the neoantigens to produce the vaccine. 

The KEYNOTE-942 study included 157 patients (50 in the pembrolizumab monotherapy arm and 107 in the combination arm). The combination showed an increase in relapse-free survival compared to standard treatment, without increasing its toxicity. In addition, a 44% reduction in the risk of recurrence or death was calculated. Taking into account the results, the mRNA-4157 vaccine in combination with pembrolizumab received the designation of innovative therapy by the American regulatory agency, the FDA (Food and Drug Administration) in February this year; as well as receiving the designation PRIME (priority medicines) by the European regulatory agency, the EMA (European Medicines Agency) in April. These denominations have been designed to accelerate the development of drugs or products intended to treat serious diseases, where preclinical data have shown substantial improvements over the available treatment.

Also, the results of a phase 1 clinical trial with an mRNA vaccine (autogene cevumeran) in combination with immunotherapy (atezolizumab anti-PD-L1) and chemotherapy (mFOLFIRINOX), as additional treatment to pancreatic cancer surgery, were published in May in the journal, Nature. This study has shown that the combination induces immune T cell activity, which may correlate with increased survival. In addition, there was a greater expression of tumour markers associated with greater survival in the group of patients who received the combination of treatments, the standard and the new treatment with mRNA. 

The results of both studies are promising, but caution is needed. Although the results of the KEYNOTE-942 study are positive, it should be noted that the statistical calculations are not entirely robust. Thus, additional trials are needed on other types of tumours to help consolidate these initial results; for example, phase 3 trials with mRNA-4157 are to be launched soon. Also of interest would be to include molecular data and the immune profile of the tumour, as well as evaluating its involvement in the response. 

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REFERENCE ARTICLES:

Harnessing the Immune System in the clínic; April 16th 2023; AACR annual Meeting 2023; Orlando. 

Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;1-7. doi:10.1038/s41586-023-06063-y