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Gene therapy effective for treatment-resistant leukaemia

27 November 2017

By Sam Sherratt

Appeared in BioNews 928

A new gene therapy for leukaemia is effective for a majority of patients who showed resistance to previous therapies.

The study, published in Nature Medicine, used a new method to treat the most common cancer found in children, pre-B cell acute lymphoblastic leukaemia (B-ALL).

The treatment uses customised immune cells to target a protein present on the surface of B-ALL cancer cells, called CD22. The customised cells, known as Chimeric Antigen Receptor (CAR) T-cells, are created by removing T-cells from a patient's own body, then genetically modifying them to target specific proteins found on the surface of cancer cells. 

The modified T-cells are then re-administered to the patient, causing their immune system attack the cancer more efficiently. Of 15 cancer patients treated in the CD22 study, 11 went into remission.

Previous CAR treatments have involved programming the T-cells to target CD19, a protein often expressed on the surface of leukaemic B-cells. These treatments have proven to be effective in many patients, but in some cases cancer cells do not express CD19 at high enough levels for them to work. 

'The idea that we could have one magic bullet is naïve,' Dr Crystal Mackall, associate director of Stanford University School of Medicine’s Cancer Institute, told the New York Times.

By targeting CD22 instead of CD19, the new therapy induced remission even in five patients who had shown resistance to the anti-CD19 treatment.

However, the results were not all positive. The new therapy induced remission in more than 70 percent of patients, but a significant number eventually relapsed as their cancer cells began to alter their presentation of CD22. 

Researchers hope to overcome this by combining therapies to target multiple proteins at once, rather than just one. Future studies will also need to consider how much of a target is needed for successful, long-lasting treatment, Dr Mackall said. 

'The take-home message is that we've found another CAR T-cell therapy that displays high-level activity in this phase-1 trial,' she said. 'But the relapse rate was also high. So this forces the field to get even more sophisticated.'

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