What Is an Individualized Neoantigen Therapy, and How Is One Made?

The short version

A melanoma trial in the news tested a treatment that does not exist until someone needs it. Each dose is made from that one person's tumor. Nobody else can be given it.

This page explains what that means, in order: what the target is, how the treatment is built, and what the practical limits are.

What a neoantigen is

Cancer cells carry mutations. Some of those mutations change a protein enough that the immune system could, in principle, tell it apart from the body's own proteins.

A protein changed in that way is called a neoantigen. "Neo" means new. It is new in the sense that it did not exist in that person before the cancer did.

Neoantigens are useful for two reasons. They are found on cancer cells and not on healthy ones, so a treatment aimed at them has a narrower target. And most of them are unique to one person's tumor, because the mutations that produced them are.

That second point is the whole reason these treatments have to be personalized.

How the treatment is built

The sequence is roughly the same across the companies working on this.

1. Surgeons remove the tumor. A piece of it is sent for genetic sequencing, along with a blood sample.
2. Software compares the two. Mutations present in the tumor but not in the person's normal cells are candidate neoantigens.
3. The candidates are ranked. Most mutations do not produce anything the immune system can see. The software predicts which ones are most likely to provoke a response, and a shortlist is chosen.
4. Those chosen targets are written into a strand of mRNA — a set of instructions.
5. The mRNA is manufactured, packaged, and given as an injection.

Inside the body, the person's own cells read the instructions and make the neoantigen proteins. The immune system meets them, learns them, and can then recognise the same features on any remaining cancer cells.

Why mRNA

The mRNA part is a manufacturing choice, not a biological one.

You could deliver these targets other ways, and researchers have tried. mRNA is attractive because changing the product means changing a sequence of letters, not rebuilding a process. The same factory can make a different treatment for the next person.

This is the same underlying technology as the mRNA COVID vaccines. It is being used for a different job. A COVID vaccine teaches the immune system to recognise a virus that everyone might meet. A neoantigen therapy teaches it to recognise features of one person's cancer.

If you have seen claims that mRNA vaccines cause cancer, we address that separately in do mRNA COVID vaccines cause "turbo cancer".

How this differs from a prevention vaccine

The word "vaccine" carries the wrong picture here.

An HPV or hepatitis B vaccine is given to healthy people to stop an infection that could later cause cancer. It is prevention, and it comes off a shelf. Cancer vaccines for prevention covers those.

A treatment vaccine is given to someone who already has cancer, or has just had it removed. The NCI describes treatment vaccines as working against cancer cells rather than against something that causes cancer.

Both are called vaccines because both train the immune system. Almost nothing else about them is alike.

Why it is given with another drug

In the melanoma trial, the personalized therapy was added to pembrolizumab, not used instead of it.

Pembrolizumab is a checkpoint inhibitor. Very roughly, tumors can switch off the immune cells that come for them, and a checkpoint inhibitor blocks that switch.

The two are meant to do complementary jobs. One shows the immune system what to look for. The other stops the tumor from shutting the response down. That is the theory the trial was built on. Immunotherapy explains both types in more detail.

The practical limits

These are the reasons a result like this does not immediately change what happens in clinics.

It needs tumor tissue. Enough of it, of good enough quality, from surgery. That rules out people whose cancer cannot be operated on.

It takes weeks to make. Each batch is one person's treatment. During that wait, the cancer is not waiting.

The target list is a prediction. Software picks which mutations are most likely to work. It can pick wrong.

It is expensive to produce. A bespoke product for one patient does not get cheaper the more people are treated, the way a mass-produced drug does.

None of these are unsolvable. All of them are unsolved.

What this does not mean

Nothing on this page says the approach works. It describes how the treatment is made.

Whether it helps people live longer is a separate question, and one that the melanoma trial has only partly answered. The result reported so far is about how long the cancer stayed away, not how long people lived. What the melanoma trial found covers what was and was not shown, and what recurrence-free survival measures explains why that distinction is the one that matters.

Individualized neoantigen therapies are not approved. They are available only inside clinical trials. Finding a clinical trial explains how to look.

Sources

• https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/cancer-treatment-vaccines
• https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoantigen
• https://www.merck.com/news/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-autogene-plus-keytruda-met-endpoints-of-recurrence-free-survival-rfs-and-distant-metastasis-free-survival-dmfs-in-patient/