Cell therapy shows promise in treating deadly childhood brain cancer

A new approach to treating deadly brain and spinal cord tumours in young people has shown promising results including clinical improvements and a possible remission in a recent human trial.

Researchers from Stanford University, who conducted the trial, tested the safety and benefits of using CAR-T cell therapy to target lethal brain and spine cancers in children.

Diffuse midline gliomas, which primarily affect children and young adults, are among the most aggressive forms of cancer with a median survival time of about one year.

Of the 11 participants involved in the recent trial, nine showed significant clinical improvements, including four who had their tumours reduced by 52 to 100 per cent.

One participant in particular, who had “diffuse intrinsic pontine glioma” (DIPG), an aggressive cancer with a five-year survival rate below one per cent, achieved a complete response, with no detectable tumour on scans so far.

However, even given the promising outcome, it is still considered “too soon to say whether he is cured”.

“This is a universally lethal disease for which we’ve found a therapy that can cause meaningful tumour regressions and clinical improvements,” Dr Michelle Monje, the trial’s lead author and a professor of neurology at Stanford Medicine, said in a statement.

“While there is still a long way to go to figure out how to optimise this for every patient, it’s very exciting that one patient had a complete response. I’m hopeful he has been cured,” she added.

How does the new treatment work for brain cancer?

Stanford Medicine researchers found in 2018 that some forms of aggressive brain and spinal cord cancer cells produce high levels of a surface marker called GD2.

They then went on to show that using GD2-targeting CAR-T cells can eradicate cancer in animal models.

The study then advanced to a human clinical trial, which is still ongoing. The chimeric antigen receptor T cells, or CAR-T cells, are developed by extracting a patient’s T cells and genetically modifying them to target a specific molecular marker found on cancer cells.

These engineered cells are then infused back into the patient’s body, where they initiate an immune response to attack the cancer.

CAR-T cell therapy has previously been approved by the US Food and Drug Administration (FDA) for treating blood cancers.

‘A path forward’

The initial findings from 11 trial participants were recently published in the journal Nature.

The trial provided evidence that the CAR-T cell therapy helped with severe symptoms caused by the tumours, including significant disabilities that develop as the disease progresses.

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“I believe there is tremendous potential. We’ve already observed striking responses to CAR T-cell therapies in both paediatric and adult brain cancers, which is excellent news given how challenging these tumours can be to treat,” Dr Stephen Bagley, an assistant professor of haematology-oncology and neurosurgery at the University of Pennsylvania, told Euronews Health.

Still, Bagley, who wasn’t involved in the study, noted that one of the main limitations of the treatment is that it isn’t “uniformly effective” and some patients’ tumours could not respond to these therapies, while others experience “remarkable responses”.

“We still don’t know enough about what factors predict success,” he said.

In the recent trial, the treatment caused some side effects such as fever and low blood pressure, as well as neurological side effects due to inflammation within the tumour.

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Bagley also explained that “toxicity” is one of the main current limitations of this therapy.

“Most of these products are associated with neurotoxicity related to the inflammation in the brain induced by the treatment,” he said, adding that they need to develop strategies to mitigate the risk and treat it when it occurs.

“Nonetheless, I think we as a field, including our patients, are willing to tolerate some transient toxicity as long as there is meaningful clinical benefit on the back end”.

The median survival among participants was 20.6 months (1.7 years) after diagnosis.

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One participant, Drew, remains alive four years post-diagnosis and became the first to achieve a complete response to the therapy.

His case has also provided hope to the researchers that this approach may provide a viable cure for aggressive brain cancers in youth.

For now, researchers are focusing on understanding the factors that distinguished the participants with the best results and are continuing to refine the therapy as additional participants enrol in the trial.

“While this trial represents progress, we still have work to do to diminish the toxicity of treatment and enhance benefit for patients,” Dr Crystal Mackall, a professor of paediatrics and medicine at Stanford, said in a statement, “but now we have a path forward”.

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Bagley added: “Our job as a field at this point is to optimise these treatments – we want to increase the proportion of patients who respond favourably and make the responses more durable”.

“I think we are making progress on these fronts, and I see a strong possibility of CAR T-cell therapies becoming approved for use in brain cancers over the next 5-10 years, and possibly sooner than that depending on how things go,” he said.