Case series of fratricide-resistant CD7-CAR T cells in T cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory (R/R) T-ALL is generally poor. In a study at the National University of Singapore, 17 R/R T-ALL patients received autologous CAR T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained MRD-negative complete remission within 1 month. The remaining patient had CD7^- T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: CRS grade 1 in ten patients and grade 2 in three patients, and ICANS grade 1 in two patients. During median follow-up of 15 months, eleven patients remained relapse-free, including all nine patients who received an allotransplant. The first patient is in remission 55 months after infusion without further chemotherapy or transplantation; circulating CAR T cell were detectable for 2 years. The authors conclude that autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL.