A novel cell therapy targeting CD7 on leukemia cells may provide an effective treatment option for patients with refractory T-cell acute lymphoblastic leukemia (ALL), according to a recent study published by Oh et al in Nature Medicine. The findings highlighted the effectiveness of a new chimeric antigen receptor (CAR) T-cell therapy.
Background
T-cell ALL accounts for approximately 10% of ALL cases in pediatric patients and 25% to 30% of cases in adolescent and young adult patients. Although 70% to 80% of pediatric patients may be cured with intensive and prolonged chemotherapy, the cure rate among adult patients remains approximately 60% or lower. Patients with relapsed or refractory T-cell ALL often have a survival rate of less than 10%.
Study Methods and Results
In the study, researchers recruited 17 patients (aged 2–72) with T-cell ALL who did not respond to chemotherapy or relapsed after treatment. The patients’ cells were reprogrammed to express an anti-CD7 CAR and then reinfused into the patients. The researchers noted the anti-CD7 CAR protein is capable of redirecting the CAR T cells to kill T-cell ALL cells that have CD7 protein on their surface. The patients were then assigned to receive the novel cell therapy at the National University Hospital in Singapore and Ospedale Pediatrico Bambino Gesù in Italy between April 2019 and October 2023.
The researchers discovered that 16 of the patients achieved complete remission within 1 month of treatment, and leukemic cells became undetectable even with ultrasensitive flow cytometry tests capable of detecting 1 leukemia cell in the background of 10,000 normal cells. The survival rate among the patients was 50%.
The same techniques were key to analyzing the CD7 expression in leukemic cells and determining patient eligibility as well as monitoring expansion and persistence of CAR T cells following infusion. The researchers highlighted that the first patient treated with the novel therapy has been in remission for 5 years without needing additional chemotherapy or a bone marrow transplant.
The treatment was reported to be well tolerated, and the side effects were mild—which was particularly notable because all patients participating in the study had a high tumor burden and had received prolonged and intensive treatment prior to CAR T-cell therapy.
Conclusions
“This CAR T-[cell] therapy is a new and promising tool to treat [patients with] T-[cell] ALL who have failed [to respond to] conventional treatment. These patients had exhausted all potentially curative options, and we are heartened that we could give them another clear chance at cure without severe side effects. We are committed to seek better cures for patients with complex and treatment-resistant cancers,” stated lead study author Bernice Oh, MBBS, MMed, MCI, a consultant in the Division of Paediatric Haematology and Oncology at the Khoo Teck Puat–National University Children’s Medical Institute at the National University Hospital.
“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,” underscored co–study author Allen Yeoh, MBBS, MMed, the VIVA-Goh Foundation Professor in Paediatric Oncology at the National University of Singapore as well as Head and Senior Consultant in the Division of Paediatric Haematology and Oncology at the Khoo Teck Puat–National University Children’s Medical Institute at the National University Hospital and the National University Cancer Institute in Singapore. “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,” he concluded.
Disclosure: This research in this study was 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, NMRC Research Training Fellowship, NMRC Clinician Scientist Award and NMRC Centre Grant, 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, and VIVA Foundation for Children with Cancer. For full disclosures of the study authors, visit nature.com.
