Targeting childhood brain tumours from within: using a smart gel to deliver immunotherapy

The challenge

Pontine diffuse midline glioma (DMG) grows deep in the brainstem, the part of the brain that controls breathing and movement, and most children live for less than a year after diagnosis. Currently, the only standard treatment is radiotherapy, which can ease symptoms but cannot cure the cancer.

There is hope that a type of immunotherapy called CAR T cell therapy could be a better option. This treatment involves taking a patient’s immune cells, modifying them in the laboratory so they can ‘see’ the tumour more clearly, and then returning them to the body to fight the cancer.  Early clinical trials of CAR-T cells in small numbers of children with DMG have shown promising signs. However, there are two major obstacles. First, the brain has a natural protective barrier that stops many drugs from entering the brain and reaching the tumour. Second, DMG tumours are very good at switching off immune cells before they can do their job. Medicines called checkpoint inhibitors can help keep immune cells active, but it is difficult to get enough of these drugs to the tumour without causing serious side effects elsewhere in the body.
 

The project

Dr Karolina Dziemidowicz and her team at University College London aim to tackle both of these problems in their new project. They are developing a gel containing CAR-T cells and checkpoint inhibitor drugs that can be safely delivered directly into the tumour through a very fine tube. Once in place, the gel is designed to slowly release both treatments in and around the tumour, keeping them exactly where they are needed. In this project, they will test whether the gel keeps the CAR-T cells healthy, releases the drugs at the right rate, and can be delivered reliably.
 

The impact

If the results are encouraging, Dr Dziemidowicz hopes to use these findings, alongside ongoing clinical trials, to support future research. In a disease where treatments have changed very little for decades, this represents an important step towards offering hope to children and families affected by DMG.