16 IN 17
patients achieved complete remission within 1 month
First
patient treated with CAR-T therapy has been in remission for 5 years
50%
of patients with relapsed or refractory T-ALL survived with CD7 CAR-T therapy
Issue 52
Nov 2024
SCIENCE OF LIFE
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 journal Nature Medicine on 3 September 20241, 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 (NUS Medicine) and the National University Health System (NUHS), the therapy was administered 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 17 patients, ranging from 2 to 72 years of age, had T-ALL that could not be eliminated with chemotherapy or had relapsed after treatment. Using technology developed in Professor Dario Campana’s laboratory at the Department of Paediatrics at NUS Medicine, the patients’ own T-cells were reprogrammed to express an anti-CD7 CAR, before being re-infused. 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 1 month, and the leukaemic cells became undetectable even with ultra-sensitive flow cytometry tests developed by Dr Elaine Coustan-Smith laboratory at NUS Medicine. These tests can detect 1 leukaemia cell in a background of 10,000 normal cells. The same techniques were key to analysing CD7 expression in leukaemic cells and determining patient eligibility as well as monitoring expansion and persistence of CAR-T cells after infusion. The first patient treated with this therapy has been in remission for 5 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.
T-ALL accounts for approximately 10% of ALL cases in children and 25 to 30% in adolescents and young adults2,3. Although 70 to 80% of children are cured with intensive and prolonged chemotherapy, the cure rate in adults remains approximately 60% or lower4.
Patients with relapsed or refractory T-ALL have less than 10% survival, while in this series, 50% survived. This fratricide-resistant CD7 CAR-T therapy is being trialled at NUH.
Dr Bernice Oh, the first author of the study and a Consultant in the Division of Paediatric Haematology and Oncology at the Khoo Teck Puat – National University Children’s Medical Institute (KTP-NUCMI), NUH, said: “This CAR-T therapy is a new and promising tool to treat T-ALL patients who have failed conventional treatment. These patients had exhausted all potentially curative options, and we are heartened that we could give them another clear chance at a cure without severe side effects. We are committed to seek better cures for patients with complex and treatment-resistant cancers.”
(Clockwise from left) Dr Esther Chan, Dr Bernice Oh and Prof Allen Yeoh, patient Viet Tai and his mother, Mdm Nguyen. Credit: National University Health System
Professor Allen Yeoh, who led the clinical application of this new technology and is Head and Senior Consultant in the Division of Paediatric Haematology and Oncology at NUH’s KTP-NUCMI and the National University Cancer Institute, Singapore, 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 the VIVA-Goh Foundation Professor in Paediatric Oncology at NUS Medicine.
This research is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Singapore Translational Research Investigator Award (MOH-000708), NMRC Research Training Fellowship (MOH-000616), NMRC Clinician Scientist Award (NMRC/CSA/003/2008 and NMRC/CSA/0053/2013) and NMRC Centre Grant (NMRC/CG/NCIS/2010), as well as the Cancer Science Institute of Singapore, National University of Singapore, the Goh Foundation, Children’s Cancer Foundation, Singapore Totalisator Board, Bone Marrow Donor Programme (Singapore) and VIVA Foundation for Children with Cancer.
Oh, B.L.Z., Shimasaki, N., Coustan-Smith, E. et al. Fratricide-resistant CD7-CAR T cells in T-ALL. Nat Med (2024). https://doi.org/10.1038/s41591-024-03228-8.
Teachey, D. T. & Pui, C.-H. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 20, e142–e154 (2019).
Raetz, E. A. et al. Outcome for children and young adults with T-cell ALL and induction failure in contemporary trials. J. Clin. Oncol. 41, 5025–5034 (2023).
Abaza, Y. et al. Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. Am. J. Hematol. 93, 91–99 (2018).
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