Improving immunotherapy for brain tumours

Our immune system is made up of lots of cells that fight off invaders like bacteria, viruses, and cancer cells in early stages. However, cancer often escapes by hiding from the immune system, or by preventing it from recognising or attacking the cancer cells. Immunotherapy treatments aim to overcome this by enhancing the body’s natural immune response to target cancer cells more effectively. This approach often has fewer side effects than traditional cancer treatments. This is because it provides a more targeted approach compared with chemotherapy and radiotherapy, which damage healthy brain tissue alongside cancer cells. While immunotherapy has shown success in cancers like melanoma, lung, and kidney cancer, progress has been limited with brain tumours.

One of the biggest challenges is the blood-brain barrier (BBB). The BBB acts like a sieve to protect the brain from harmful substances. This barrier makes it difficult to develop drugs that can get into the brain to reach the tumour.

Brain tumour cells also have clever ways of escaping immunotherapy treatment. They can produce signals that ‘switch off’ the immune system. This allows them to escape attack and continue to grow.

There are several different types of immunotherapy. Here’s an overview of the science behind different immunotherapies, and some of the ways we are funding research at the forefront of improving immunotherapies for people facing a brain tumour diagnosis.

Cancer vaccines

Dendritic cells are an important type of cell in our immune system. Their job is to break down tumour cells and present tumour cell signals on their surface. This allows other immune cells to recognise the tumour and attack.

There are clever ways scientists can alter immune cells to make them better at doing their job. One approach is dendritic cell vaccines, which involve removing both tumour cells and blood from the patient. The dendritic cells are separated from the blood sample and exposed to the tumour cells. This teaches the dendritic cells to recognise specific signals on the tumour cells. The altered dendritic cells are then re-introduced to the bloodstream and can teach other immune cells to target and destroy the tumour.

In 2022, a phase III clinical trial found that a dendritic cell vaccine, called DCVax®-L,  may prolong the lives of people diagnosed with a new or recurrent glioblastoma. Read our blog on DCVax®-L to find out more.

CAR-T Cell Therapy

Another key type of immune cell for fighting disease are known as T cells. T cells recognise anything in the body considered ‘alien,’ such as cancer cells, and destroy them.

Along a similar vein to dendritic cell vaccines, CAR-T cell therapy involves taking some of the patient’s own T cells, extracted from a blood sample. Scientists then modify the cells in the lab to help target tumour cells. They are also multiplied so that there are lots of them. Finally, the cells are then returned to the bloodstream and now act as trained ‘sniffer dogs’ that can hunt down and kill cancer cells more efficiently.

CAR-T cells have proven very effective in many types of cancer, especially in blood cancers such as leukaemia. We have not seen this success in brain tumours yet. This is due to the genetic make-up of brain tumour cells. Their genes can look and behave very differently, even within different parts of the same tumour. This means that scientists would need to engineer the T cells to attack multiple different types of tumour cell for a single person.

Funded by our Future Leaders grant scheme, Dr Chris Mount’s research is aiming to improve CAR-T cell therapies for high grade gliomas – a common type of aggressive brain tumour with no current cure,

Checkpoint Inhibitors

Our healthy cells have signals on them to tell our immune cells not to attack them. However, some cancers can hijack this approach, tricking the immune system into not attacking the tumour cells. They do this by producing too many signals that dampen the immune system and not enough signals that activate it to kill the tumour cells. Checkpoint inhibitors are drugs that can block these signals. This removes the tumour cells’ disguise, so that our immune cells can find and destroy them.

We recently funded Professor Khuloud Al-Jamal’s research aiming to make the immune system more effective at fighting glioblastoma.

Oncolytic viruses

We know that viruses are really good at getting into our cells to spread infections like the flu. Scientists have found a way that we can harness this ability to target cancer cells. These viruses are known as oncolytic, or ‘smart viruses’. They are specially engineered to only attack and kill tumour cells, leaving healthy brain cells untouched.

Our new Future Leader, Dr Emily Bates, is looking at developing ‘smart viruses’ to help combat glioblastoma.

Cytokines

Cytokines are proteins that help immune cells communicate and work together to fight disease. They act like messengers, telling immune cells when and where to attack infections and cancer cells. An important group of cytokines called interleukins can help the immune system in different ways. Some interleukins can amplify the immune system response. Equally, some types of interleukin can dampen the immune response.

Through our Quest for Cures grant, we awarded Dr Jun Ishihara and his team £1.5 million to develop an immunotherapy drug using interleukin-12 (IL-12) for recurrent glioblastoma tumours.

There are many avenues to explore to ensure that we unlock the potential of immunotherapy for brain tumours. We need the best researchers to find the most effective, kind and targeted treatments for those facing a brain tumour diagnosis.