Why Moderna and Merck’s cancer vaccine is a breakthrough for mRNA

WASHINGTON – The announcement by Moderna and Merck & Co that a messenger RNA-based cancer vaccine had lowered the recurrence rate for melanoma in a final-stage trial is a watershed moment for cancer vaccine research.

It is the first time that an mRNA-based cancer vaccine has succeeded in a large-scale study.

While the companies did not disclose details about the results, the success has bolstered hopes that mRNA-based shots could some day play a broad role in fighting one of the world’s leading causes of death. 

The results also signal a second act for a technology that encountered widespread scepticism during the Covid-19 pandemic among those angered by vaccine mandates or uneasy about the shot’s rapid development.

The technology continues to get pushback today, including from influential figures like US Health Secretary Robert F. Kennedy Jr.

But investors and many in the scientific community were cheered by the new findings.

Shares of Moderna rose 177 per cent the day the news was announced. 

The results could boost enthusiasm for cancer vaccine research in general.

Such vaccines have been pursued for decades by scientists, but they have frequently had lacklustre results in all-important human trials. 

How do mRNA vaccines work?

Traditionally, vaccines have worked by exposing the immune system to a weakened or inactivated form of a disease-causing organism, or to a harmless piece of one, so that the body learns to recognise and fight it. 

Vaccines using mRNA take a different approach.

They temporarily turn some of the body’s cells into tiny vaccine-making factories.

The shots contain laboratory-made mRNA, which carries instructions telling those cells to make a particular protein associated with the disease.

The immune system recognises that protein and produces antibodies to attack it.  

In the case of Covid-19 vaccines, the mRNA instructs cells to make the spike protein found on the surface of SARS-CoV-2.

That trains the immune system to recognise the spike and respond quickly if it later encounters the virus.

How can an mRNA vaccine treat cancer?

It turns out that essentially the same mRNA technology used for Covid-19 and the flu – which is also being studied for other infectious diseases – can be employed to train the immune system to attack cancer.

This type of vaccine is not used to prevent cancer, but would instead be deployed to treat cancer already present, often to prevent a recurrence in patients who have had surgery.

Such vaccines contain mRNA with instructions for making fragments of mutated proteins produced by cancer cells. Once inside the body, the mRNA instructs cells to produce the mutated protein fragments, the so-called neoantigens. The goal is to prompt the immune system to recognise the mutated proteins, triggering an immune response against the cancer. 

Why are mRNA vaccines personalised?

Cancer cells typically contain mutated proteins that, in theory, can be recognised by the immune system.

But no two tumours are exactly the same, and mutations can vary widely among patients with the same type of cancer.

Over the years, it has proven difficult to come up with a one-size-fits-all vaccine that consistently generates a strong immune system response against tumours, although researchers are still working on it.

Among other problems, tumours might be able to evade an immune response targeted against a single distinguishing feature.

To create personalised vaccines, scientists take samples from an individual patient’s tumours and put them through an algorithm to determine which mutations are most likely to result in an immune response.

For the Merck and Moderna shot, the companies can put up to 34 mutations into a personalised shot, which is sent back to the patient’s doctor to administer to the patient. 

“Thirty-four is quite a lot of chances, of shots on goal,” said Jane Healy, head of oncology early development at Merck, which has been working with Moderna on the cancer vaccine approach for more than a decade.

That ensures the vaccine is “covering a sufficient amount of the spectrum of a patient’s cancer”, said Healy.

How are mRNA cancer vaccines different from other cancer treatments?

Cancer vaccines work in a very different way from other cancer treatments such as chemotherapy, targeted pills and immunotherapy.

Chemotherapy poisons fast-dividing cells, while newer targeted medicines block particular growth-promoting proteins on cancer cells.

Best-selling immunity-boosting drugs already on the market, including Merck’s Keytruda and Opdivo from Bristol Myers Squibb, are antibodies that disable a key method that cancer cells use to evade an immune response against them.

But off-the-shelf immunotherapy drugs do not prepare the immune system to recognise and target an individual’s specific tumour.

This is what personalised cancer vaccines aim to do, which technically are treatments, not preventative shots. 

Because it is thought this approach will work well against small volumes of cancer cells, many vaccines, such as the Merck-Moderna trial in melanoma, aim to prevent recurrences in patients who are at high risk of the cancer coming back after surgery.

Much is still unknown about the melanoma results, including the magnitude of the benefit.

Findings from the vaccine trial will be reported at an upcoming scientific meeting.

In particular, scientists do not yet know whether people who got the vaccine will live longer, and the trial is continuing in order to gather long-term results. 

What other diseases are mRNA treatments being tested against?

In addition to melanoma, Merck and Moderna are testing their personalised cancer approach for lung cancer, bladder tumours and kidney cancer.

Meanwhile, Germany’s BioNTech and Swiss pharmaceutical giant Roche Holding are testing their own mRNA-based personalised cancer vaccine to treat both pancreatic cancer and colon cancer.

BioNTech is working on a different mRNA technology that uses a standardised shot to treat patients with advanced lung cancer and head and neck cancer. 

Rare diseases are another potential use for mRNA technology.

Moderna is testing its mRNA technology to treat metabolic diseases including propionic acidemia and methylmalonic acidemia. BLOOMBERG