The resurgence of mRNA: vaccines are delivering the first major breakthroughs in the fight against cancer

Whilst melanoma made the most sensational headlines, it is pancreatic cancer that probably offers the most poignant illustration of the potential – and the limitations – of this technology. A report published in April told the story of an American patient who was diagnosed with pancreatic cancer in 2020: a disease in which only one in four patients survives the first year.

The woman joined a clinical trial at the Memorial Sloan Kettering Cancer Centre led by the surgical oncologist Vinod Balachandran, who has been studying rare ‘super-survivors’ to pancreatic cancer to understand why their immune systems are able to recognise the tumour as a foreign body. Following the surgical removal of the tumour, the tissue was sent to Germany, where BionTech’s laboratories transformed it into a bespoke vaccine, which was returned to the patient within a few weeks and administered alongside immunotherapy and chemotherapy.

The course of treatment was not straightforward – the chemotherapy proved almost intolerable, to the extent that it had to be discontinued after just a few sessions – but six years on, the patient is alive and shows no signs of the disease. This is not an isolated case: out of 16 participants in the pilot study, eight developed a marked immune response to the vaccine, and seven of these eight were still alive six years later – data which were subsequently presented at the American Association for Cancer Research conference. These numbers are too small to be definitive – which is why a larger, multicentre trial has already begun – but they point the way forward: if an mRNA vaccine can trigger a lasting response against one of the most difficult cancers to treat, the principle could be replicated elsewhere.

The Moderna-Merck approach to melanoma and the MSK-BioNTech approach to pancreatic cancer share the same philosophy: total personalisation, with a different vaccine for each patient. It is a powerful approach but one that is difficult to scale up industrially, both in terms of production times and costs.

For this reason, a second line of research is being developed in parallel: that of ‘generalised’ or ready-to-use vaccines, designed to target molecules shared by many patients with the same type of cancer, without the need for individual customisation. A researcher at the University of Florida has taken this approach a step further, testing an mRNA vaccine in mouse models that does not encode any specific tumour antigen but non-specifically stimulates the production of a protein – PD-L1 – which makes tumours more vulnerable to immunotherapy. The idea, in this case, is not to hit the target with surgical precision, but to ‘awaken’ the immune system quickly and broadly, thereby gaining precious weeks compared to the time it takes to produce a personalised vaccine.

A third line of research, perhaps the most surprising, comes from an analysis carried out on over a thousand cancer patients being treated with immune checkpoint inhibitors: those who had received an mRNA Covid vaccine in the 100 days prior to starting treatment showed a significantly better response to the anti-cancer drugs, to the extent that, for some subgroups, survival rates almost doubled. The authors’ hypothesis is that mRNA acts not only as a targeted agent but also as a general alarm signal that alerts the entire immune system – an observation that has already led to the launch of a new clinical trial specifically designed to test this hypothesis.

The context in which these results have emerged has not been straightforward. Over the past eighteen months, mRNA technology applied to oncology has faced intense political pressure in the United States, fuelled by scepticism within parts of the administration towards mRNA vaccines in general – a legacy of the controversies surrounding Covid vaccines. Among the most critical moments were: a request from the National Institutes of Health to disclose all mRNA-related funding; a proposal to cut the National Cancer Institute’s funding by over 40 per cent; the cancellation of a $590 million agreement with Moderna for a pandemic influenza vaccine; and the suspension – later revoked following protests from the scientific community – of the FDA’s review of Moderna’s mRNA influenza vaccine.

Several researchers have reported that their confidence in the sector has wavered, at least temporarily, and some projects – such as a study into an experimental vaccine for a rare paediatric brain tumour, which had already been approved but lacked actual funding – remain stuck in administrative limbo. In recent months, however, the flow of federal funding appears to have resumed, with dozens of new grants awarded and official statements identifying mRNA cancer vaccines as a research priority. Meanwhile, the most advanced programmes – led by the melanoma programme – are now primarily supported by private capital and industrial partnerships, which are less exposed to fluctuations in public budgets.

Today’s results on melanoma and pancreatic cancer are not the end of the road, but the first solid confirmation of a principle that has been pursued for twenty years: teaching the immune system to recognise a tumour as a foreign entity, using the same technological platform as the Covid vaccines. Several issues remain to be resolved: the industrial scalability of personalised treatments, the price (which Moderna has not yet set), confirmation of the benefits in terms of overall survival — not just recurrence-free survival — and the continued support from the public and regulators over time.

If accelerated approval were to be granted – as some analysts believe is plausible as early as 2027 – the melanoma vaccine could become the first personalised mRNA cancer treatment available on a large scale, paving the way for trials already underway for other solid tumours – lung, bladder, kidney and pancreas – which have shown encouraging, albeit still preliminary, results in recent months.