Investigating Immune cell fitness to determine patient response to Chimeric Antigen Receptor (CAR)T-Cell therapy

End of project summary

Main messages

Recent advances in cancer therapy have recognised that killer cells called T cells within the body’s immune system can be altered so that they can target and kill cancer cells. This new treatment is called Chimeric Antigen Receptor T cells (CART) and cures about half of the patients with advanced blood cancer, but there are some serious side effects and the remaining 50% of patients who don’t respond may die within 6 months. The reasons why this expensive treatment fails is unclear and there is currently no way for doctors to predict which patients will be treated successfully.

This research study was conducted at Cardiff University Hospital Wales by a new Cellular Therapy research team of scientists, nurses, doctors and patient contributors. The research focused on how ‘fit’ a patient’s immune cells were and whether they were able to expand and increase in number inside the body to fight the tumour. 

The team found that there were more ‘fit’ T cells in patients that responded to CART treatment. These ‘fitter’ cells had more power to metabolise energy, could seek and find tumour cells through the bloodstream and expanded rapidly in the body resulting in a good outcome. Those patients that didn’t respond so well had exhausted T cells and we could detect these even before treatment. 

Our patient involvement group were involved in every step of the research process and discussed the best way to approach new patients, collection of samples, the patient burden and areas for new research including monitoring brain toxicity and quality of life. We are now actively pursuing these as spin out projects.

What now?

The results of this study will help us to better tailor treatments to suit individual patients so they can avoid unnecessary toxicity issues. This would improve the results for patients, in terms of their health and their quality of life.  

Our findings will now be validated in a much larger set of patients across the UK with our partner hospital sites to confirm which patients may need more careful monitoring after treatment. We are also now designing a new treatment that may boost the fitness of immune cells for those that don’t do so well and we are working with clinical teams to explore how we can better protect the fitness of patient T cells either by collecting and storing patient cells early or by pre-treating cells with protective drugs.