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
Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Nat Med. 2024 Dec;30(12):3687-3696. doi: 10.1038/s41591-024-03228-8. Epub 2024 Sep 3.
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.
T细胞急性淋巴细胞白血病(T-ALL)在治疗后复发或对化疗耐药时难以治疗;复发或难治性T-ALL患者的预后通常较差。我们报告了一组17例此类患者的病例系列,他们接受了表达抗CD7嵌合抗原受体(CAR)T细胞和抗CD7蛋白表达阻断剂(PEBL)的自体CAR T细胞,后者可防止CAR T细胞自相残杀。尽管白血病负担高且CAR T细胞剂量低,但17例患者中有16例在1个月内达到微小残留病阴性完全缓解。其余患者在输注前有CD7 T-ALL细胞,输注后持续存在。毒性较轻:10例患者发生1级细胞因子释放综合征,3例患者发生2级;2例患者发生1级免疫效应细胞相关神经毒性综合征。11例患者无复发(中位随访15个月),包括所有9例接受同种异体移植的患者。首例患者在输注后55个月处于缓解状态,无需进一步化疗或移植;可检测到循环CAR T细胞达2年。淋巴细胞清除后再生的T细胞缺乏CD7表达,呈多克隆性且对SARS-CoV-2疫苗有反应;CD7免疫细胞与CAR T细胞消失同时重新出现。总之,自体抗CD7 PEBL-CAR T细胞具有强大的抗白血病活性,可能是治疗T-ALL的有效选择。