Fratricide-resistant CD7 CAR-T therapy by NUS shows promise in treating relapsed or refractory T-cell leukaemia
A novel cell therapy that targets CD7 on leukaemia cells offers a potentially effective solution for patients suffering from T-cell acute lymphoblastic leukaemia (T-ALL) who have run out of traditional treatment alternatives. This study, published on 3 September 2024 in the medical journal Nature Medicine, highlights the success of an innovative chimeric antigen receptor (CAR) T-cell therapy.
Created by researchers and medical professionals from the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) and the National University Health System (NUHS), this therapy was administered to 17 patients from April 2019 to October 2023. The treatments took place at the National University Hospital (NUH) in Singapore and Ospedale Pediatrico Bambino Gesù in Rome, Italy.
The 17 patients, aged between two and 72 years, were diagnosed with T-ALL that had either not responded to chemotherapy or had returned after initial treatment. Utilizing a technology developed in Professor Dario Campana’s lab at NUS Medicine’s Department of Paediatrics, the researchers reprogrammed the patients’ own T cells to express an anti-CD7 CAR, which was then reintroduced to the patients. This anti-CD7 CAR protein guides the CAR T-cells to attack T-leukaemia cells displaying CD7 on their surface.
Remarkably, 16 out of 17 patients entered complete remission within one month, with leukaemic cells becoming undetectable using highly sensitive tests that can identify one leukaemia cell among 10,000 normal cells. These tests were developed by Ms. Elaine Coustan-Smith’s lab at NUS Medicine. These testing methods were crucial in analyzing CD7 levels in leukaemic cells to determine patient eligibility, as well as monitoring the growth and persistence of CAR-T cells post-infusion. The first patient treated with this therapy has remained in remission for five years, without the need for further chemotherapy or a bone marrow transplant.
The treatment was well-tolerated, with only mild side effects reported, especially considering that all participant patients had severe tumour burdens and had previously undergone intense treatment before receiving CAR-T therapy.
T-ALL represents about 10% of all acute lymphoblastic leukaemia (ALL) cases in children and 25 to 30% in adolescents and young adults. While 70 to 80% of children may be cured with extensive chemotherapy, the cure rate for adults is around 60% or less.
For patients with relapsed or refractory T-ALL, the survival rate is less than 10%, whereas this treatment series showed a survival rate of 50%. The fratricide-resistant CD7 CAR-T therapy is currently being evaluated at NUH.
Dr. Bernice Oh, the lead author of the study and a Consultant in Paediatric Haematology and Oncology at the Khoo Teck Puat – National University Children’s Medical Institute (KTP-NUCMI), NUH, stated: “This CAR-T therapy represents a new and promising approach for T-ALL patients who have not succeeded with conventional treatments. These individuals had run out of all potential curative options, and we are excited that we could offer them a renewed chance at a cure without severe side effects. We remain dedicated to finding improved treatments for patients with complex, treatment-resistant cancers.”
Professor Allen Yeoh, who oversaw the clinical implementation of this new technology and serves as Head and Senior Consultant in the Division of Paediatric Haematology and Oncology at NUH’s KTP-NUCMI and the National University Cancer Institute, Singapore, remarked: “While we celebrate this significant development, we recognize that this is just the beginning of an exciting journey. There is much to learn scientifically and medically to maximize the use of CD7 CAR T-cells. Each patient in this study has taught us invaluable lessons. Ultimately, for each team member, it’s priceless to see patients smile and have another chance after reaching remission.” Professor Yeoh holds the VIVA-Goh Foundation Professorship in Paediatric Oncology at NUS Medicine.
This research received support from the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd, the NMRC Singapore Translational Research Investigator Award (MOH-000708), the NMRC Research Training Fellowship (MOH-000616), the NMRC Clinician Scientist Award (NMRC/CSA/003/2008 and NMRC/CSA/0053/2013), and the NMRC Centre Grant (NMRC/CG/NCIS/2010), along with backing from the Cancer Science Institute of Singapore, National University of Singapore, the Goh Foundation, Children’s Cancer Foundation, Singapore Totalisator Board, the Bone Marrow Donor Programme (Singapore), and the VIVA Foundation for Children with Cancer.
