By Jon Moore, November 2, 2026
Thérapies à base d’ARN : présent et avenir
Cet article continue en anglais...
The story of how messenger RNA technology rapidly delivered highly effective prophylactic vaccines in the SARS-CoV-2 pandemic is foundational. Programmes developed by BioNTech SE and Moderna Inc used nucleoside base modifications to develop vaccines that successfully protected against the virus. The base modification technology was developed by the scientists Katalin Karikó and Drew Weissman based on their insights into how synthetic mRNA interacted with the immune system - discoveries that led to their receipt of the Nobel Prize in Physiology or Medicine in 2023.
At the same time, the ability of the mRNA vaccines to curb the pandemic was only possible due to existing infrastructure at BioNTech and Moderna which had been created to support their long-standing plans to develop therapeutic mRNA-based vaccines for cancer. BioNTech's programme started in 2008 while Moderna's was underway by 2015 at the latest.
These mRNA cancer vaccine initiatives are now bearing fruit. In August, Moderna and its partner, Merck & Co Inc, announced positive results for a Phase 3 trial in more than 1,100 adjuvant melanoma patients. The results showed that a personalised cancer vaccine regimen added to pembrolizumab, the standard of care, benefitted patients.
This followed results from a preceding Phase 2b study, where the addition of a personalised vaccine reduced recurrence or death by 49% up to five years out'. Moderna's success represents a spectacular demonstration of the power of an mRNA medicine beyond infectious diseases.
Moderna, BioNTech and their pharma partners have made significant investments in logistics and infrastructure to meet the challenge of building personalised mRNA cancer vaccines. In Moderna's case, these have been scaled for late-stage clinical trials. Manufacture commences with DNA and RNA sequencing of patient tumours, proceeds via selection of the most promising antigens (up to 34 in the Moderna cancer vaccines), and then follows by the synthesis of a DNA construct, in vitro transcription to produce mRNA and finally its encapsulation into, or complex formation with, defined lipids to form a nanoscale formulation for delivery to patients. The objective is to treat patients with their first dose of therapeutic vaccine within four weeks of accessing the tumour material. Currently this is typically achieved within six weeks.
It is universally acknowledged that cancer vaccines have generally disappointed in pivotal trials. Therefore, Moderna's positive results in randomised Phase 2 and Phase 3 trials will be attributed by many to either mutated neantigens being more effective than those previously pursued by the field, or to LNP-pseudouridine-modified mRNA being a uniquely high-performing modality. However, it can equally be argued that the clinical success of the Moderna/ Merck partnership has been driven by selecting the right indication, setting and partners.
Deploying a fully individualised therapeutic cancer vaccine in an adjuvant setting is a demanding task which mRNA vaccines have shown they can meet. However, similar timelines from surgery/biopsy to first dose have been delivered by DNA vaccines (Geneos Therapeutics Inc) and viral vectors (e.g. Transgene SA and Nouscom AG).
A key, if not unique, advantage of lipid nanoparticles (LNPs) for the therapeutic vaccine role is the ability to re-dose with the same entity multiple times (typically nine doses are used in the BioNTech and Moderna clinical trials).
There is no counterpart of the toggling between adenoviral vector mediated priming and vaccinia virus vector mediated boosting deployed by Nouscom. mRNA is also devoid of the theoretical possibility of DNA-based vectors integrating into patient cells. Finally, while adjuvanted peptide-based vaccines could be deployed quickly and at scale, the diverse peptides required for a personalised product will differ considerably in their physicochemical properties. This could encourage the prioritisation of manufacturability rather than antigen quality in the choice of agents taken forward.
BioNTech continues to use native uridine-containing mRNA in its cancer vaccine portfolio and while this platform currently lacks a clear Phase 2 victory in a randomised trial, it should not be discounted. Published data indicate that the BioNTech cancer vaccines can deliver very strong T cell responses. Peak levels of vaccine-induced T cell clones can reach 20% of total T cells?. Moreover vaccine induced T cell clones can be very persistent, which has been linked to long term control of pancreatic adenocarcinoma in early Phase 1 trials.
A pivot to off-the-shelf cancer vaccines
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