CAR-T cell therapy in brain tumour treatment

Treatments for brain tumours haven’t improved in decades. We are committed to changing this by funding pioneering research to find a cure for this devastating disease.

Brain tumours are a complex group of diseases and there are researchers around the world trying to understand them better and find kinder, more effective treatments.

One such treatment that is high on the research agenda is CAR-T cell therapy.

In this blog we will discuss:

• What CAR–T cell therapy is
• How CAR–T cell therapy can be used to treat brain tumours
• Recent CAR–T cell therapy research

What is CAR–T cell therapy?

CAR-T cell therapy is a type of immunotherapy.

Immunotherapy harnesses the power of the immune system to fight cancer. Our immune system is designed to find and kill cancer cells. But these cells often have clever ways of avoiding the body’s natural defence against cancer.

CAR-T cell therapy uses T cells. These are cells in the immune system that already have an important role in fighting cancer. However, in some cancers, T cells are unable to recognise cancer cells as harmful. So scientists teach these cells how to recognise the cancer by engineering them in the laboratory – making CAR-T cells.

They are produced from a patient’s own T-cells in their blood. These cells are collected and modified by scientists so they can recognise cancer cells. The modified cells are then infused back into that person to can kill the cancer.

CAR-T cells are very specific to a person’s tumour because they have been trained to recognise specific cells. However, there are side effects linked to this treatment resulting from the immune system killing the tumour cells. Despite this, CAR-T cells have proven incredibly effective in many cancers, especially blood cancers such as leukaemia.

CAR–T cell therapy and brain tumours

Because CAR-T cells show such great promise in other types of cancer, brain tumour researchers are hopeful that one day this technology will offer a new set of treatments for brain tumours. We are currently funding Dr Christopher Mount in our Future Leaders programme. He is researching ways to improve CAR-T cell therapies for gliomas, which are a common type of brain tumours with few treatment options.

To date, this therapy has been difficult to use in glioma treatment. This is because the cells within a person’s tumour can be so diverse. It is therefore challenging to engineer T cells to recognise and attack all the different types of tumour cells within these tumours. Also, glioma cells are well known for their ability to reduce the effect of the immune system to protect themselves from attack.

Recent research

Researchers at Mass General Cancer Centre in Massachusetts, including our Future Leader Dr Christopher Mount, have started a clinical trial to test CAR-T cell therapy against brain tumours. The phase I trial is evaluating the safety of this treatment option for people with newly diagnosed and recurrent glioblastomas – a particularly devastating type of glioma.

The trial, known as INCIPIENT, is recruiting patients at Massachusetts General Hospital Cancer Centre in the USA.

Early analysis of the first three patients enrolled have shown positive results, with glioblastomas responding to treatment within days of the CAR-T cell infusion.

Critically, all patients tolerated the treatment well, which was the most important objective in this early safety trial. Similar to other CAR-T cell trials, patients experienced fevers after the cells were delivered.

Although their tumours initially shrank significantly, all three patients eventually had tumour recurrence within 1 to 6 months of treatment.

For brain tumour researchers and patients, this is a very promising result despite the recurrence of these tumours. Having shown that this new CAR-T cell therapy can be given safely, the researchers in Boston can now explore ways to improve outcomes for patients on this trial, such as changing how the these cells are delivered and potentially delivering additional doses of therapy.

In the laboratory, these early results motivate ongoing research to understand why the tumours recurred. They also show the need for continuing efforts to understand the biology of this disease so that future CAR-T cell and other immunotherapies can be even more effective.

This is an exciting next step for CAR-T cell therapies in glioblastoma. This work is led by a team of scientists and physicians who deeply understand the challenges of this disease and are committed to designing new strategies to overcome those obstacles. While it is still too early to judge whether this will be an effective treatment for other glioblastoma patients, the early data are promising and the entire team is eager to build upon this initial experience in the clinic and in the laboratory!”

Dr Christopher Mount, one of The Brain Tumour Charity’s Future Leaders