| Autor: |
Oh, Bernice L. Z., Shimasaki, Noriko, Coustan-Smith, Elaine, Chan, Esther, Poon, Limei, Lee, Shawn H. R., Yeap, Frances, Tan, Lip Kun, Chai, Louis Y. A., Le Bert, Nina, Tan, Nicole, Bertoletti, Antonio, Chen, Siew Peng, Del Bufalo, Francesca, Becilli, Marco, Locatelli, Franco, Yeoh, Allen E. J., Campana, Dario |
| Zdroj: |
Nature Medicine; 20240101, Issue: Preprints p1-10, 10p |
| Abstrakt: |
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 T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (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 minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7−T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: cytokine release syndrome grade 1 in ten patients and grade 2 in three patients; immune effector cell-associated neurotoxicity syndrome grade 1 in two patients. Eleven patients remained relapse-free (median follow-up, 15 months), 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 cells were detectable for 2 years. T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7+immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL. |
| Databáze: |
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