Promising cell therapy offers hope for relapsed or refractory T-cell leukaemia

Published: 05 Oct 2024

From left: Members of the research team, Dr Esther Chan, Dr Bernice Oh, and Prof Allen Yeoh. (Credit: NUHS)

A new cell therapy, targeting CD7 on leukaemia cells, gives a potentially effective treatment for patients with T-cell acute lymphoblastic leukaemia (T-ALL) who have exhausted all standard treatment options. Published in the prestigious medical journal Nature Medicine on 3 September 2024, the study highlights the effectiveness of a new chimeric antigen receptor (CAR) T-cell therapy.

Developed in-house by researchers and clinicians from the Yong Loo Lin School of Medicine, National University of Singapore and the National University Health System (NUHS), the therapy was given to 17 patients between April 2019 and October 2023 at the National University Hospital (NUH) in Singapore and Ospedale Pediatrico Bambino Gesù in Rome, Italy.

All the 17 patients, ranging from two to 72 years of age, had T-ALL that could not be eliminated with chemotherapy or had relapsed after treatment. Using a technology developed in Professor Dario Campana’s laboratory under the Department of Paediatrics at NUS Medicine, the patient’s own T cells were reprogrammed to express an anti-CD7 CAR, and then re-infused into the patients. The anti-CD7 CAR protein redirects the CAR T-cells to kill T-leukaemia cells that have CD7 protein on their surface.

Notably, 16 of the 17 patients achieved complete remission within one month, and leukaemic cells became undetectable even with ultra-sensitive flow cytometry tests that can detect one leukaemia cell in the background of 10,000 normal cells, developed by Ms Elaine Coustan-Smith’s laboratory at NUS Medicine. The same techniques were key to analyse CD7 expression in leukaemic cells and determining patient eligibility as well as to monitor expansion and persistence of CAR-T cells after infusion. The first patient treated with this therapy has been in remission for five years, without needing additional chemotherapy or a bone marrow transplant.

The treatment was well-tolerated, and side effects were mild, given the fact that all patients enrolled had a high tumour burden and had received prolonged and intensive treatment prior to CAR-T therapy.

Professor Allen Yeoh, who led the clinical application of this new technology and is the VIVA-Goh Foundation Professor in Paediatric Oncology from the Department of Paediatrics at NUS Medicine, said, “While we celebrate this wonderful milestone, we are only at the beginning of this exciting journey. There is a lot of scientific and medical enquiry to understand how to better use CD7 CAR T-cells. Each patient, in this series, taught us a lot. Ultimately, for every member of our team, seeing each patient smile and given another chance, after achieving remission, is priceless.” Prof Yeoh is also Head and Senior Consultant in the Division of Paediatric Haematology and Oncology at NUH’s Khoo Teck Puat – National University Children’s Medical Institute and the National University Cancer Institute, Singapore.