Using CAR-T cell therapy to treat diffuse midline glioma

Thursday 19 April 2018

Recently published research shows that CAR-T cell therapy, a type of immunotherapy, has the ability to treat diffuse midline glioma

Diffuse midline glioma, formerly known as diffuse intrinsic pontine glioma (DIPG)*, is a type of primary, high-grade brain tumour occurring in children. It is one of the most fatal paediatric brain tumours, with less than 1% of patients surviving beyond five years.

The dismal prognosis of diffuse midline glioma can be attributed to its location, the brain stem. The brain stem is a difficult to access region of the brain, making it impossible to surgically remove the tumour using current technology.

The current standard of care used to treat diffuse midline glioma is radiation therapy. However, radiation therapy is not a cure and only provides relief from symptoms temporarily, making it essential to develop more effective treatments for this aggressive tumour type.

The research recently published in Nature Medicine was led by Dr Michelle Monje and Professor Crystal Mackall at Stanford University School of Medicine, and showed that chimeric antigen receptor T (CAR-T) cell therapy could help kill DMG cells.

CAR-T cells are synthetically engineered T cells, which are a type of immune cell. CAR-T cells can recognise cancer cells and direct the patient's own immune system to fight their cancer.

The researchers found that approximately 80% of diffuse midline gliomas had a molecule called GD2 on the surface of the tumour cells. They then engineered T cells to specifically target this molecule.

The study showed that when mice whose brainstems had been implanted with human diffuse midline glioma cells were treated with the GD2-targeted CAR-T cells, the majority of the tumours were eliminated.

“I was pleasantly surprised with how well this worked," said Dr Monje. “We gave CAR-T cells intravenously, and they tracked to the brain and cleared the tumor. It was a dramatically more marked response than I would have anticipated."

However, CAR-T cell therapy has had mixed results in treating solid tumours. The researchers noted that some mice experienced dangerous levels of swelling in the area surrounding the tumour as a result of the immune response triggered by the therapy.

CAR-T therapy has been approved by the FDA to treat blood cancers such as childhood leukaemia and some lymphomas. This means that it could be translated into clinical use for brain tumours faster relative to developing new therapies.

*Following the 2016 revision to WHO classification, this tumour is now known clinically as “Diffuse Midline Glioma- Pontine Location H3 K27M.

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