Cancer vaccine breakthrough: Why it matters even if it doesn't prevent cancer

Merck and Moderna have reported encouraging Phase 3 results for a personalised mRNA cancer vaccine in melanoma when used with pembrolizumab. The treatment aims to stop recurrence after surgery, though peer-reviewed data and longer follow-up are still awaited.

In Short

• The treatment is given after surgery to lower relapse risk
• Tumour mutations are analysed to create personalised neoantigen targets for immunity
• Pembrolizumab is used alongside the vaccine to strengthen the anti-cancer response

The word “vaccine” usually means a shot given to a healthy person to prevent an infection. So why is a treatment being described as a cancer vaccine if it does not prevent cancer from developing in the first place?

The question has gained attention after Merck and Moderna announced encouraging Phase 3 results for their personalised mRNA cancer vaccine, intismeran autogene, in melanoma, a very aggressive form of skin cancer, although the findings are yet to be published in a peer-reviewed medical journal.

According to the World Health Organisation – International Agency for Research in Cancer (WHO-IARC), about 3.3 lakh new melanoma cases are diagnosed annually, resulting in nearly 60,000 deaths and the incidence rates are the highest in North America, Europe and Australia with fair-skinned populations at the highest risk.

In India, melanoma is rare – just 0.3–0.5 % of about 15 lakh new cancers diagnosed every year.

The vaccine, given along with the immunotherapy pembrolizumab – better known by its brand name Keytruda – met key trial endpoints for recurrence-free survival and distant metastasis-free survival.

The development is significant because the vaccine is being tested to reduce the chances of cancer returning in people who have already been treated for it.

That matters because even after a tumour is removed, microscopic cancer cells can sometimes remain in the body and eventually cause the disease to return and the recurrence – also driven by genetic factors or treatment resistance in many cases – remains a major clinical hurdle.

Alarmingly, global cancer cases are rising rapidly with over 2 crore new diagnoses and about 1 crore deaths annually, projected to nearly double to 3.5 crore cases by 2050.

THE TARGET IS RECURRENCE

The Merck-Moderna vaccine is being studied as an adjuvant treatment, an additional therapy given after surgery, when the visible tumour has been removed, to lower the risk of recurrence.

In personalised cancer vaccination, doctors analyse an individual's tumour to identify mutations that are unique to, or characteristic of, that cancer. These can produce abnormal markers called neoantigens. The mRNA vaccine is designed to train the immune system to recognise these targets.

Earlier results in melanoma showed that adding the personalised vaccine to pembrolizumab reduced the risk of recurrence and distant spread compared with pembrolizumab alone. The Phase 3 INTerpath-001 trial has now reported that it met its key recurrence-free and distant metastasis-free survival endpoints.

“This improvement in recurrence-free and distant metastasis-free survival is extremely valuable, as recurrence is one of the main challenges in treating melanoma,” pointed out Dr Trinanjan Basu, head of radiation oncology with HCG Cancer Hospital, Mumbai.

But he cautioned that the findings need to be interpreted carefully until the complete peer-reviewed Phase 3 data and longer follow-up, including overall survival, are available.

So, this is not a vaccine that a healthy person takes to ensure they never get melanoma. It is being developed for people who have already had cancer and remain at risk of it returning.

WHY CALL IT VACCINE?

The difference is in what the immune system is being trained to recognise.

A conventional vaccine prepares the immune system to recognise a virus or bacterium before it causes disease. A therapeutic cancer vaccine uses the same basic principle of immune training, but its target is cancer.

The personalised vaccine effectively gives the immune system a molecular “wanted poster” of the patient's tumour. If microscopic cancer cells remain after surgery, the aim is for the immune system to recognise and destroy them before they can grow into another tumour.

Dr Nitish Ranjan Acharya, surgical oncologist with Manipal Hospital, Bhubaneswar, put it simply: the vaccine “teaches the immune system what to attack in that person’s cancer”, while immunotherapy helps it fight those cells more effectively.

That is why the term vaccine is used: it creates a targeted immune response, rather than preventing cancer from occurring in the first place.

THE BIGGER PROMISE

The excitement is not limited to melanoma. Researchers are testing cancer vaccines against several difficult-to-treat cancers, including lung, bladder, pancreatic, head and neck cancers and brain tumours.

Pancreatic cancer is particularly important because it is often diagnosed late and remains difficult to treat. An early trial of a personalised mRNA vaccine in pancreatic cancer produced encouraging results, although it was a small study and needs confirmation in larger trials.

Other approaches are also being explored. BioNTech's BNT113 is an mRNA-based treatment being studied for HPV16-positive head and neck cancers. Another candidate, BNT211, combines a treatment that uses genetically modified immune cells with an RNA vaccine designed to boost their activity.

For pancreatic cancer and other tumours driven by particular mutations, Elicio Therapeutics is developing ELI-002.

It is designed to target mutant KRAS – a mutation found in several solid cancers – and direct the immune response towards cancer cells carrying it. The treatment is being studied in Phase 2 trials after early research showed sustained T-cell responses and reductions in cancer-related biomarkers.

There is also interest in using artificial intelligence (AI) to design cancer vaccines. Evaxion Biotech's EVX-05 is an AI-designed, off-the-shelf vaccine candidate being developed for glioblastoma and other brain cancers.

The approaches are different, but the broad idea is similar: make the immune system better at identifying cancer cells and then use that response to keep the disease under control.

Dr Basu said the field is moving rapidly from experimental therapy towards a potentially clinically useful tool, with the greatest potential likely to come from combining personalised cancer vaccines with immunotherapy and other targeted treatments.

But this is not yet a universal cancer vaccine.

Different cancers, and even tumours in the same patient, can have different mutations. Personalised vaccines also have to be developed for individual patients, raising questions about cost, manufacturing time and access.

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