Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia

Area of Science:

• Oncology
• Immunotherapy
• Hematology

Background:

• CD7 is a key target for CAR T-cell therapy in T-cell acute lymphoblastic leukemia (ALL).
• Previous studies showed supportive results for base-edited anti-CD7 CAR (BE-CAR7) T cells.
• BE-CAR7 T cells utilize triple C→T deamination for TCRαβ, CD52, and CD7 knockouts.

Purpose of the Study:

• To evaluate the safety and efficacy of BE-CAR7 T cells in pediatric and adult patients with relapsed or refractory T-cell ALL.
• To assess the rate of complete remission and the feasibility of proceeding to allogeneic hematopoietic stem-cell transplantation.
• To determine secondary outcomes including remission duration, disease-free survival, and overall survival.

Main Methods:

• A phase 1 study administered BE-CAR7 T cells to children (≤16 years) and adults with relapsed/refractory T-cell ALL.
• Patients received lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab prior to BE-CAR7 T-cell infusion.
• Patients achieving remission by day 28 proceeded to allogeneic hematopoietic stem-cell transplantation.

Main Results:

• BE-CAR7 T cells were administered to 11 patients (9 children, 2 adults).
• No unacceptable adverse events were observed during lymphodepletion and BE-CAR7 infusions; circulating CAR7 T cells were detected in all patients.
• 82% of patients achieved deep remission, allowing them to proceed to stem-cell transplantation; 64% remained in remission at 3-36 months post-transplant.
• Leukemia with loss of CD7 expression occurred in 2 patients; viral reactivations were frequent post-transplantation.

Conclusions:

• Universal BE-CAR7 T cells induced leukemic remission in most patients with relapsed/refractory T-cell ALL.
• BE-CAR7 T-cell therapy facilitated successful allogeneic hematopoietic stem-cell transplantation in the majority of treated patients.
• BE-CAR7 T cells represent a promising therapeutic strategy for T-cell ALL, warranting further investigation.