How Does the New Cancer Vaccine Work? It’s More Personal Than You Might Think

A cancer vaccine that is different for every patient

Traditional vaccines are generally standardized. Millions of people can receive the same vaccine.

A personalized cancer vaccine works differently.

Scientists start by studying an individual patient’s tumor. They look for genetic mutations that can produce abnormal markers, known as neoantigens, that may help the immune system distinguish cancer cells from healthy cells.

The most promising targets are selected and used to create a treatment specifically for that patient’s cancer.

In other words, two people with the same type of cancer may not receive exactly the same personalized vaccine.

Their tumors may be different, which means the targets selected for their treatment may also be different.

This is the big shift behind personalized cancer vaccines: instead of looking for one target shared by many patients, researchers can look for what makes one patient’s tumor unique.

Why did older cancer vaccine approaches struggle?

The idea of using the immune system to fight cancer is not new. Scientists have been studying therapeutic cancer vaccines for decades.

But many earlier approaches faced a major challenge. They often focused on shared tumor markers, meaning scientists tried to identify one target that could be used across many patients with a particular cancer.

The problem is that cancer is highly diverse. Even tumors classified as the same cancer can have different mutations and different biological characteristics. A target that is important in one patient’s tumor may not be the best target in another person’s tumor.

Personalized neoantigen vaccines take a different approach.

Instead of asking: “What do these tumors have in common?”

Researchers ask: “What makes this particular tumor different?”

Advances in genetic sequencing and vaccine technology have made that approach increasingly practical.

Why the new melanoma results matter

The recent Moderna and Merck news is important because the personalized treatment, intismeran autogene, has now produced positive topline results in a large Phase 3 melanoma trial.

The INTerpath-001 trial included 1,137 patients with surgically removed, high-risk melanoma. The personalized treatment was studied in combination with pembrolizumab, better known as Keytruda. According to the companies, the Phase 3 trial met its primary endpoint of recurrence-free survival and a key secondary endpoint of distant metastasis-free survival.

However, there is an important limitation to keep in mind: the full Phase 3 data, including the exact effect sizes, have not yet been publicly presented. That means we know the trial met important goals, but we do not yet know the complete numerical picture.

Earlier results were already encouraging

Before the new Phase 3 results, researchers had already seen promising findings in an earlier Phase 2b trial called KEYNOTE-942.

At five years, the personalized vaccine combined with pembrolizumab (Keytruda) was associated with a:

49% reduction in the risk of recurrence or death

and a:

59% reduction in the risk of distant metastasis or death, compared with pembrolizumab alone.

These are significant numbers, but they need to be interpreted correctly. They are from the earlier Phase 2b trial, not the newly announced Phase 3 trial. That distinction is one reason the new Phase 3 announcement is so important. The larger study provides a more advanced stage of clinical testing, but the detailed numerical results from that trial have not yet been publicly released.

Why combine the vaccine with pembrolizumab?

The personalized vaccine is not necessarily doing all the work by itself. Its role is to help the immune system recognize specific features of a patient’s cancer. Pembrolizumab is an immunotherapy drug known as a checkpoint inhibitor. It works differently by blocking signals that can limit the immune system’s ability to attack cancer.

The combination is designed to address two different challenges:

• • The personalized vaccine helps show the immune system what to look for.
  • Pembrolizumab helps support the immune response against cancer.

This combination approach may be an important reason personalized cancer vaccines are being studied alongside existing cancer immunotherapies.

Could this work for other cancers?

Melanoma is currently the most advanced example in the recent Moderna and Merck program, but researchers are also studying personalized cancer vaccine approaches in other cancers. These include:

• • Non-small-cell lung cancer
  • Bladder cancer
  • Kidney cancer
  • Pancreatic cancer
  • Gastric cancer

This does not mean the treatment has been proven to work in all of these cancers. Each cancer presents different biological challenges, and positive results in melanoma do not guarantee the same results elsewhere. Still, the expansion of research into multiple tumor types shows that scientists see potential beyond a single form of cancer.

So, are we close to a cancer vaccine?

The answer depends on what you mean by “cancer vaccine.” We are not close to a single universal shot that prevents everyone from getting cancer. That is not what this treatment is. But we may be getting closer to personalized treatments that use the unique biology of an individual patient’s tumor to help the immune system recognize and fight cancer.

For the melanoma treatment now making headlines, several important steps still remain. The full Phase 3 data still need to be presented. Overall survival data are still being followed. Regulators would also need to review the treatment before it could become an approved standard therapy. So this is not a cure, and it is not yet an approved cancer treatment.

But the recent results represent an important step for a scientific idea that has been developing for years.

Cancer treatment may increasingly move away from simply asking: “What type of cancer do you have?” And toward another question:

“What makes your cancer unique?”

That is the promise behind personalized cancer vaccines.

Sources

National Cancer Institute (NCI)
Cancer Treatment Vaccines
Neoantigen Vaccines Keep Kidney, Pancreatic Cancer at Bay

ClinicalTrials.gov / U.S. National Library of Medicine
INTerpath-001 Clinical Trial, NCT05933577

American Society of Clinical Oncology (ASCO)
KEYNOTE-942 Five-Year Update

Merck & Moderna
INTerpath-001 Phase 3 announcement

Reuters
Moderna, Merck vaccine cuts recurrence and spread of melanoma, raising new treatment hope