Funded by the Little Princess Trust and administered by CCLG
Lead investigator: Professor John Anderson, University College London Great Ormond Street Institute of Child Health
Award: £264,501.34
Awarded May 2025
The challenge
CAR T-cell therapy is a cancer treatment that takes blood cells (T-cells) from a patient and uses genetic engineering to add the CAR protein. This makes the cell able to recognise and kill cancer cells. CAR T-cell therapy has been used to treat incurable blood cancers in children, but is generally less successful against solid tumours. One reason for this is that when a CAR T-cell enters a tumour, it gets overactivated, becomes exhausted and stops working.
Professor John Anderson’s lab at University College London Great Ormond Street Institute of Child Health has designed an ‘OFF-switch’ CAR T-cell that can be temporarily turned off, allowing the CAR T-cells to rest and recover. To ensure that the cancer can’t grow, the researchers are working on a second type of CAR T-cell that would become active while the OFF-switch CAR T-cells are resting.
However, CAR T-cells need to be produced individually for each patient. Prof Anderson’s CAR T-cell therapy would require two personalised treatments to be created, which would be very expensive for hospitals.
The project
In this project, Prof Anderson aims to develop and refine a method that can create both types of CAR T-cell at the same time. Instead of using standard approaches like genetically engineered viruses to insert the CAR gene into T-cells, the researchers hope to use a newer technique called CRISPR/Cas9.
This involves cutting the T-cells DNA and then getting the T-cell to fill in the gap with new DNA based on a ‘template’. If the researchers can give a sample of T-cells two templates – an OFF-switch CAR and the new CAR – then the sample should contain a mix of the two different options. This would essentially produce two types of CAR T-cell for the price of one. There are a number of different ways to do this, so the researchers need to find the most effective option.
The impact
Developing a ‘2-for-1’ method of producing the combined CAR treatment is essential for lowering the manufacturing costs for clinical trials. This research could support the development of cheaper and more effective CAR T-cell therapy for high-risk solid tumours, many of which have limited treatment options.
The Little Princess Trust
This project was funded by The Little Princess Trust. They fund research projects in partnership with CCLG, combining CCLG's research funding and grant management expertise with The Little Princess Trust's fantastic fundraising to support world-class scientific research.