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

Recent advances in cancer therapy have recognised that killer T cells within the body’s immune system can target cancer cells. A novel approach called chimeric antigen receptor (CAR)-T cell therapy which engineers killer T-cells from the blood of patients to kill the patient’s own tumour cells is provided on the NHS for some blood cancers and is being delivered to patients in Wales for the first time over the last year.

While this remarkable therapy cures about half of patients with advanced lymphoma, the remaining 50% of patients relapse and die within 6 months (at a cost of up to £500,000 per patient) and there is currently no way of predicting which patients to treat. The reasons why CAR-T cell therapy fails is unclear but may involve the ‘fitness’ of the T cells being engineered as these patients tend to be heavily pre-treated with other chemotherapies. This could mean either that the CAR-T cells don’t expand inside the body or that they don’t last very long there.

We will explore key immune T cell behaviours that are considered important for their anti-cancer activity:

1) Their ability to grow and divide before and after treatment

2) The ability to travel through the blood stream and reach the correct tumour site in the body

3) The types of killer T cells present in the CAR-T product and how they interact with the tumour and surrounding cells (microenvironment) after they are infused into the patient.

We will compare how lymphoma patient immune cells differ to normal healthy immune cells along the treatment pathway to see if patients should have their cells preserved earlier for use at a later date.

Our feasibility study aims to use excess patient samples at serial timepoints before and after CAR-T treatment to develop a panel of biomarkers which can identify which patients will produce effective CAR-T cell products and improve the quality of the killer T cells made. We will co-ordinate a multidisciplinary team of scientists, clinical colleagues and patient/public groups to develop and communicate our findings at a local and national level, increasing our potential for patient impact.

Achieving these goals would greatly benefit patient outcomes and quality of life by tailoring the best treatment for the individual patient. This timely project has the potential to save a considerable amount of healthcare resources by providing quality data to map the best treatment pathway for lymphoma patients in Wales.