采用双阳性(CD56/CD16)扩增自然杀伤细胞的过继免疫疗法治疗复发或难治性急性髓系白血病患者:一项概念验证研究。
Adoptive immunotherapy with double-bright (CD56 /CD16 ) expanded natural killer cells in patients with relapsed or refractory acute myeloid leukaemia: a proof-of-concept study.
机构信息
Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
出版信息
Br J Haematol. 2021 Dec;195(5):710-721. doi: 10.1111/bjh.17751. Epub 2021 Sep 7.
Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56 /CD16 ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (10 -10 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.
急性髓系白血病(AML)患者的五年生存率为 28.7%。自然杀伤(NK)细胞具有抗白血病活性。在这里,我们报告了巴西一家学术中心对 13 例高危复发/难治性 AML 患者进行重复输注双阳性(CD56/CD16)扩增 NK 细胞的一系列研究。NK 细胞来源于 HLA 单倍体供体,使用 K562 饲养细胞扩增,经过修饰后表达膜结合白细胞介素-21。患者接受 FLAG 治疗后,将冷冻的 NK 细胞解冻,并在三个剂量组中每周三次输注,共输注六次。主要目标是安全性和可行性。次要终点包括首次输注后 28-30 天的总反应(OR)和完全反应(CR)率。患者接受了中位数为 5 线的治疗,7 例具有中间或不良细胞遗传学特征,3 例伴有同时性中枢神经系统(CNS)白血病,1 例伴有同时性 CNS 真菌病。未观察到剂量限制性毒性、输注相关发热或细胞因子释放综合征。观察到 78.6%的 OR 和 50.0%的 CR,包括 3 例 CNS 疾病患者的反应和 CNS 真菌病的清除。在高危复发/难治性 AML 患者中,在强化化疗后安全地给予多次输注扩增的冷冻 NK 细胞,结果令人鼓舞。