Individualised Neoantigen Therapy (INT)

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Individualised Neoantigen Therapy (INT)

What is an Individualised Neoantigen Therapy (INT)?

An individualised neoantigen therapy or INT uses a persons’ own melanoma cells to create a treatment that can help their body’s natural defence (immune system) to recognise, attack and kill their melanoma. This is known as a personalised cancer treatment because it identifies and adapts the specific characteristics of a person’s cancer to try to make an effective treatment for them.

These treatments are personalised cancer vaccines.

DNA

How do INTs work?

Cancer cells are different from normal cells as they have changes within their DNA (the building instruction manual of all cells in the human body) called mutations.  These mutations within the cancer cells can create abnormal proteins called neoantigens, which are not usually seen in normal cells (antigens are targets for the immune system). The neoantigen proteins on the surface of melanoma cells can allow the body’s immune system to recognise the melanoma cells as foreign and therefore try to attack and kill them.

These neoantigen mutations are often unique to each person’s melanoma, and it’s one of the reasons why patients who have been diagnosed with the same type of cancer and who have received the same type of treatment may have different responses.

Scientists therefore think if they can pinpoint these neoantigens in an individual person’s melanoma in the laboratory and make a treatment that can replicate the way they are able to create a helpful response from the immune system, then when this treatment is given back to a patient it can guide the immune system to attack and kill any melanoma cells that are present more effectively.

 

How are scientists developing an INT to treat melanoma?

There are different processes to develop an INT and you may hear them referred to as personalised cancer treatment, or sometimes cancer vaccines.

One such treatment that is being explored in melanoma is an mRNA-based INT.

What is mRNA?

Messenger Ribonucleic Acid (mRNA) is a genetic material that copies instructions from cellular DNA (the building instruction manual of all cells in the human body) and uses them to make proteins that carry out different functions in the body.

mRNA molecules can be thought of like a template for all of the building materials for cells in the body, they help make proteins for the cells and once the protein has been made and can do its job in the body, the mRNA can be destroyed or removed (discarded).

How can mRNA be used to create an INT?

Scientists think that the main characteristics of mRNA can be used to help create an INT:

  1. mRNA instructions can be engineered from the melanoma cells in a laboratory to be able to make specific neoantigen proteins.
  2. Shortly after the cells of the body use the mRNA to make a neoantigen protein, the mRNA is destroyed. It doesn’t stay in the body, and it can’t interact with the person’s DNA, or permanently change it.

How do patients receive Individualised Neoantigen Therapy?

Making an INT follows a very specialised process. To be able to have their melanoma treated by an INT, it is important that patients have available tissue (cells) from their melanoma tumour that can be removed to send to the laboratory to make the treatment.

In an ongoing INT clinical trial, all patients will receive standard adjuvant immunotherapy treatment for 1 year.  2 out of 3 people on the trial will also be assigned to receive the INT, so even if you are on the trial, you may not receive the INT as this trial is comparing standard treatment to standard treatment plus the INT.  If it is planned that you will receive the INT, this will be given (in addition to the standard immunotherapy) once it has been manufactured in the laboratory, for 6 months during the immunotherapy treatment period.  It is thought this combination of treatment helps to activate the immune system to enable it to identify and destroy any remaining melanoma cells in the body after surgery, and this is being tested further.

What are the potential benefits and side effects of INT?

The potential benefits of INT over other treatments, is that it helps the immune system identify, target and kill only melanoma cells, and not healthy ones, meaning that side effects from using the INT should be minimal.

As this is an experimental treatment, it can also come with its challenges:

  • All patients need to have enough melanoma tissue to be able to make the INT in the laboratory, and earlier clinical trials suggest that there are about one quarter to one third of otherwise suitable people who don’t have enough tissue.
  • The tissue needs to be of a good enough quality to make the neoantigens – so far, we know that about 10-15% of people are in this situation – this can only be checked in the facility that makes the INT – your local team cannot tell you this up front.
  • Laboratories are required to be able to make INTs for lots of patients at the same time and needs to be taken into consideration as it is a complex process, and only specific laboratories can be used.

What is the future for INTs?

There is a lot of interest to advance clinical trials in the area of personalised cancer treatment and INTs in particular, and pharmaceutical companies are dedicated to further research into this.

For further details of current trials that are available using an INT check our Melanoma TrialFinder News for updates.