Second generation CAR T-cell therapy trialled in patients

A new CAR T-cell therapy developed by scientists at UCL has fewer 'toxic' side-effects and is more durable, targeting and killing cancer cells for longer, concludes a Phase I clinical trial of patients at University College London Hospitals (UCLH). Researchers say the findings offer new hope to adult patients with 'relapsed B-cell acute lymphoblastic leukaemia' (r/r B-ALL), for which there is currently no approved 'curative' treatment available. Patients typically have further chemotherapy and the prognosis is poor. For the ALLCAR19 trial, published in the Journal of Clinical Oncology , 20 adult patients with relapsed B-ALL had their own T cells genetically modified with CAT-41BB-Z, a new type of CD19* CAR, which has been named obe-cel. Like all CD19 CAR T-Cell therapies, this treatment programmes immune T cells to make an artificial protein called a CD19 chimeric antigen receptor (CAR) on their surface, directing them to specifically recognise cancerous cells. However, in designing obe-cel, scientists in Dr Martin Pule's lab at UCL Cancer Institute - in work that is supported by the National Institute for Health Research UCLH Biomedical Research Centre (BRC) - aimed to overcome two common constraints associated with existing CAR T-cell therapies. The ALLCAR19 Chief Investigator Professor Karl Peggs, Honorary Clinical Professor at UCL Cancer Institute and Director of the Sir Naim Dangoor Centre for Cellular Immunotherapy at UCLH, explained: " While CAR T therapy is very effective for some patients, current CAR T-cell treatments have limitations.