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NZ Invention To Enhance Safety Of CAR T And Other Cell Therapies

An innovative 'safety switch' for CAR T-cell therapy, designed at the Malaghan Institute and recently patented, has the potential to significantly enhance the safety and accessibility of this cutting-edge cancer immunotherapy and other cell therapies.

Developed by postdoctoral researcher Dr Patricia Rubio-Reyes, the safety switch means that in the unlikely event that a patient who receives CAR T-cell therapy experiences severe side effects, a brake can be applied on CAR T-cell activity.

“This ability to stop potential toxicity to CAR T-cell treatment will further improve the safety profile of a treatment which already has a strong safety record,” says Dr Rubio-Reyes.

CAR T-cell therapy is a type of cancer immunotherapy that involves extracting a patient’s immune cells and genetically modifying them, to recognise and eliminate their cancer cells.

Parallel to its clinical trial of a new CAR T-cell therapy for B-cell non-Hodgkin lymphoma, the Malaghan Institute’s CAR T-cell research programme is focusing on improving the safety and effectiveness of current CAR T-cells and expanding this cutting-edge technology to treat a wider range of cancers, including solid tumours.

“In solid cancers such as lung cancer or melanoma, the cancer cells accumulate in a mass meaning the inner cells of the tumour are difficult to target. Addressing this may require a higher dose of CAR T-cells so the presence of a safety switch would be even more important,” says Dr Rubio-Reyes.

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“It also means it is more likely to be offered as a therapeutic option to patients with early-stage cancers rather than as a last resort when other options have been exhausted.”

The invention is a modified version of a naturally occurring protein called CD20, which is found on a type of immune cell called B-cells.

“What sets this safety switch apart from other similar inventions is its reliance on a naturally occurring protein, while the minor modifications remove its ability to signal unforeseen effects on other cells in the body, making it safer,” says Dr Rubio-Reyes.

“By effectively neutralising the protein, its only function is to tag the modified therapeutic cells for identification and destruction if desired.”

The modified CD20 protein can be incorporated into a CAR T-cell construct so that, if needed, the CAR T-cells can be targeted for destruction by the immune system upon injection of a specific antibody.

Dr Rubio-Reyes says that because it allows the easy detection of CAR T-cells in the body, it also provides an easy method to check if they are still in the body weeks, months or even years after the patient receives them.

The safety switch has wide-reaching potential for other adoptive cell therapies which involve extracting a patient’s cells, modifying them in the lab and reintroducing them back into the patient.

“Currently adoptive cell therapies are being used as a revolutionary approach to cancer therapy, however, there is potential for this to be applied to other diseases,” says Dr Rubio-Reyes.

Dr Rubio-Reyes was named as a KiwiNet Emerging Innovator this year for the invention, a programme which provides financial support and mentorship to build industry connections and the knowledge needed to understand the commercial potential of her invention.

“I want this safety switch to make cutting-edge therapies safer, providing more people with currently incurable conditions a path to recovery.”

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