Promising results for new CAR T-cell therapy for leukaemia

A clinical trial to investigate a novel CAR T-cell therapy developed at UCL Cancer Institute - which is designed to target cancer cells more quickly and cause less side effects - has shown very promising results for children with previously incurable acute lymphoblastic leukaemia (ALL).

In the CARPALL trial, which included patients at University College Hospital, 12 out of 14 participants with ALL cleared their disease after three months and five patients remain leukaemia-free after receiving the CAR T treatment, results published today in Nature Medicine show.

Patients also experienced less of a harmful side effect of CAR T treatment known as cytokine release syndrome (CRS).

The trial is testing a new kind of CAR T therapy in children and young adults with relapsed ALL. It is being led by Professor Persis Amrolia and Dr Sara Ghorashian at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health.

The study forms part of UCLH and UCL’s portfolio of CAR T cell studies, which is the largest in Europe, with underpinning support from the National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre.

In CAR T therapy, immune cells (T-cells) are engineered to contain a molecule called a chimeric antigen receptor (CAR) on their surface which can specifically recognise cancerous cells. In the CARPALL study, the patient’s own T cells are modified to contain a new type of CAR molecule known as CAT-19, which was developed in Dr Martin Pule’s laboratory at the UCL Cancer Institute.

The modified CAR T-cells were used to treat 14 patients with relapsed ALL at GOSH, Manchester Children’s Hospital and UCLH.

ALL affects around 400 children a year in the UK and, while most patients are curable with standard treatments like chemotherapy and transplant, in some patients the disease comes back (relapses) despite maximal treatment. CAR T-cells have shown great promise for relapsed ALL - the most common cause of cancer death in children in the UK.

In the study laboratory experiments showed that, compared to other CAR T therapies, the CAT-19 CAR T cells were able to grow better after encountering leukaemia cells. In patients, high numbers of the CAT-19 CAR T-cells were still present in the blood after the cancer had been cleared, enabling the body to keep fighting against the leukaemia even years after treatment.

Dr Pule said: “Our pre-clinical studies of this new therapy suggested that CAT-19 CAR T-cells would engraft better and it is gratifying to see this replicated in patients.”

Patients receiving CAR T therapies often experience CRS as the immune system becomes overactive attempting to fight the cancer cells. It can cause patients to be admitted to intensive care and can lead to death.

To avoid this, the CAR T therapy used in the CARPALL trial has been designed so that it interacts with its target on the surface of cancer cells more rapidly than other similar therapies.

This means that while CAR T-cells can still kill leukaemia cells efficiently, the cells cause less activation of the immune system and therefore fewer dangerous side effects.