The ‘meCAR-T’ system, developed by scientists at City of Hope, acts as updatable software that reprogrammes immune cells in real time to overcome tumour mutations and prevent relapses

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Researchers at City of Hope Medical Centre, one of the leading centres for cancer research and treatment in the United States, have developed an innovative ‘plug-and-play’ technology that allows chimeric antigen receptor T-cells (CAR-T cells) to be genetically modified even after they have been administered to the patient. This new platform increases the flexibility of treatment by allowing immune cells to be monitored in real time and redirected to combat different types of tumours.

Although CAR-T cell immunotherapy has revolutionised oncology by reprogramming the patient’s own defences to track down and destroy malignant cells, current treatments have significant limitations due to their inflexibility. At present, once the reprogrammed cells have been reintroduced into the bloodstream, it is not possible to adapt them.

This situation, as the researchers explain, means that as tumours evolve and develop mechanisms to evade the immune system, CAR-T cells lose their effectiveness, paving the way for tumour survival and relapses. To address this problem, Drs John Williams and Christine Brown redesigned these cells so that they can bind to a small molecule called ‘meP’, giving rise to the new ‘meCAR-T’ cells.

‘Tumours adapt to CAR-T therapies, leading to treatment failure and cancer relapse’

More specifically, the system functions as a modular platform that allows various components to be attached to immune cells depending on therapeutic needs. Through this mechanism, CAR-T cells can not only be tracked and stimulated to grow, but also expand their ability to recognise a wider range of cancer cells. With this breakthrough, researchers have succeeded in programming new operational functions into immune cells, improving control over how they locate and attack tumour tissue.

Regarding the mechanism of action of this technology, Dr John Williams, co-lead author of the study and director of the Central X-ray Crystallography Laboratory at City of Hope, explains that “tumours adapt to CAR-T therapies, leading to treatment failure and cancer relapse. To remain effective, our therapies must also adapt, which is why we have created a system that allows us to reconfigure these powerful anti-cancer agents as the tumour progresses”.

In the same vein, Dr Williams compares the technology to updating an electronic device, noting that, “just as a software update adds new features to a phone after you’ve bought it, Meditope technology allows us to send new instructions to the CAR-T cells that are already inside the patient’s body.”

‘The key to this platform lies in its flexibility, as rather than rigidly integrating all functions into a single CAR-T cell, we can use protein adaptors to add new capabilities as and when required’

For her part, Dr Christine Brown, co-lead author and deputy director of the T-Cell Therapy Research Laboratories at the same institution, emphasised that “the key to this platform lies in its flexibility; rather than rigidly integrating all functions into a single CAR-T cell, we can use protein adaptors to add new capabilities as required. This improves the ability to overcome tumour heterogeneity and other barriers that limit the efficacy of these therapies in solid tumours.”

The researcher adds that the scientific community is very hopeful about this new cellular control tool, noting that “it is an approach that could be applied to many different types of cancer and to other conditions for which CAR-T therapies are being developed.”

The research team’s next step will be to translate these findings into clinical practice. Two Phase I clinical trials are currently being prepared to assess both the safety and biological activity of meCAR-T cells in patients with solid tumours and acute myeloid leukaemia. With this breakthrough, City of Hope is consolidating its position at the forefront of cell therapy, a field in which it has already treated more than 2,000 patients in clinical trials and where it administers nearly 90 per cent of its CAR-T treatments on an outpatient basis.