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

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

Developed in-house by researchers and clinicians at the Yong Loo Lin School of Medicine at the 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, aged 2 to 72 years, had T-ALL that could not be cleared by chemotherapy or had relapsed after treatment. Using technology developed in the laboratory of Professor Dario Campana in the Department of Pediatrics at NUS Medicine, the patient’s own T cells were reprogrammed to express an anti-CD7 CAR and then reinfused into patients. The anti-CD7 CAR protein redirects CAR T cells to kill leukemia T cells that have the CD7 protein on their surface.

Notably, 16 of 17 patients achieved complete remission within a month and leukemia cells became undetectable even with ultra-sensitive flow cytometry assays capable of detecting a leukemia cell in the context of 10,000 normal cells, developed by the laboratory of Elaine Coustan-Smith at NUS. Medicine.

The same techniques were essential for analyzing CD7 expression in leukemia cells and determining patient eligibility, as well as monitoring CAR-T cell expansion and persistence after infusion. The first patient treated with this therapy was 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 that all enrolled patients had high tumor burden and received prolonged and intensive treatment prior to CAR-T therapy.

T-ALL accounts for approximately 10% of ALL cases in children and 25-30% in adolescents and young adults2,3. Although 70 to 80 percent of children are cured with intensive, prolonged chemotherapy, the cure rate in adults remains about 60 percent or less.

Patients with relapsed or refractory T-ALL have a survival rate of less than 10%, whereas in this series, 50% survived. This fratricide-resistant CD7 CAR-T therapy is being tested at NUH.

Dr. Bernice Oh, first author of the study and consultant at the Division of Pediatric Hematology and Oncology at Khoo Teck Puat — National University Children’s Medical Institute (KTP-NUCMI), NUH, said: “This CAR therapy -T is a novel and promising tool to treat T-ALL patients who have failed conventional treatment. These patients have exhausted all potentially curative options, and we are encouraged that we can give them another clear chance at recovery without serious side effects. seek better cures for patients with complex and treatment-resistant cancers.

Professor Allen Yeoh, who led the clinical application of this new technology and is head and principal consultant of the Division of Pediatric Hematology and Oncology at KTP-NUCMI of NUH and the National University Cancer Institute of 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 research to understand how to better use CD7 CAR T cells. Each patient in this series has taught us a lot. of our team, seeing each patient smile and have another chance, after achieving remission, is priceless.