A novel CD7-directed CAR-T cell therapy has demonstrated remarkable efficacy in patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL), offering renewed hope for those who have exhausted standard treatment options. Developed by the National University Health System (NUHS) and the National University of Singapore's Yong Loo Lin School of Medicine (NUS Medicine), the fratricide-resistant therapy targets CD7, a protein expressed on T-ALL cells.
Clinical Efficacy
In a study spanning from April 2019 to October 2023, 17 patients aged 2 to 72 years with chemotherapy-resistant or relapsed T-ALL were treated at the National University Hospital (NUH) in Singapore and the Ospedale Pediatrico Bambino Gesù in Rome, Italy. The CAR-T cell therapy involves reprogramming patients' T cells to express an anti-CD7 CAR, which are then re-infused to target and destroy CD7-expressing leukemia cells. Remarkably, 16 out of 17 patients achieved complete remission within one month, as confirmed by ultra-sensitive flow cytometry capable of detecting minimal residual disease (MRD). The first patient treated has maintained remission for five years without further chemotherapy or bone marrow transplant.
Mechanism of Action and Trial Design
The CD7 CAR-T cell therapy leverages technology developed in Professor Dario Campana’s laboratory at NUS Medicine. The engineered CAR-T cells specifically target the CD7 protein on the surface of T-leukemia cells, leading to their destruction. The ultra-sensitive flow cytometry tests, developed by Ms. Elaine Coustan-Smith’s laboratory at NUS Medicine, played a crucial role in assessing CD7 expression and monitoring CAR-T cell persistence post-infusion. The study enrolled patients with relapsed or refractory T-ALL who had failed conventional treatments. While specific dosing regimens were not detailed, the therapy was reported to be well-tolerated, with only mild side effects observed despite the patients' high tumor burden and extensive prior treatments.
Expert Commentary
According to Dr. Bernice Oh, consultant at the National University Children’s Medical Institute (KTP-NUCMI), NUH, and the Paediatric Haematology and Oncology Division, "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 cure without severe side effects. We are committed to seeking better cures for patients with complex and treatment-resistant cancers."
Implications for T-ALL Treatment
T-ALL is an aggressive form of leukemia that can be difficult to treat, especially in patients who relapse or are refractory to chemotherapy. The development of CD7 CAR-T cell therapy represents a significant advancement in the field, offering a potential curative option for these high-risk patients. The high rate of complete remission and the long-term remission observed in the first patient treated highlight the therapy's potential to transform the treatment landscape for relapsed/refractory T-ALL.
