炎症性骨髓微环境导致获得性骨髓衰竭综合征。 CK0801 是一种同种异体 T 调节性 (Treg) 细胞治疗产品，有可能中断这种持续的炎症循环并恢复造血功能。在 CK0801 Treg 细胞的这一 1 期剂量递增研究中，我们招募了患有骨髓衰竭综合征且对治疗反应欠佳的患者。我们招募了 9 名中位年龄为 57 岁（范围为 19 至 74 岁）的患者，其潜在诊断为再生障碍性贫血 (n=4)、骨髓纤维化(n=4)，或发育不良性骨髓发育不良 (n=1)。患者之前接受过三种骨髓衰竭综合征治疗。 CK0801的起始剂量水平为每公斤理想体重1 × 106 (n=3)、3 × 106 (n=3)和10 × 106 (n=3)个细胞。未进行淋巴细胞清除。 CK0801在门诊给药，未出现输液反应，未出现3级或4级严重不良反应，也未出现剂量限制性毒性。 12 个月时，CK0801 在四名骨髓纤维化患者中的三名（两名有症状缓解，一名有贫血缓解，一名疾病稳定）和四名再生障碍性贫血患者中的三名（三名有部分缓解）中诱导客观缓解。四分之三的输血依赖患者在基线时实现了输血独立。尽管观察时间被限制在0.9至12个月，但没有观察到感染增加，没有转化为白血病，也没有死亡。在既往治疗的患者中，CK0801没有表现出剂量限制性毒性，并显示出疗效证据，提供了证据以炎症为目标治疗骨髓衰竭的概念。 （由 Cellenkos Inc. 资助；ClinicalTrials.gov 编号，NCT03773393。）。

An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis.In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes.We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 106 (n=3), 3 × 106 (n=3), and 10 × 106 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths.In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).