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现货型异基因 NK 细胞治疗 COVID-19

英文原题:Off-the-shelf allogeneic natural killer cells for the treatment of COVID-19.

查看英文原题

Off-the-shelf allogeneic natural killer cells for the treatment of COVID-19.

PubMed 2024/10/28(内容时间) Mol Ther Methods Clin Dev Q2 · IF 5(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

自然杀伤(NK)细胞数量和功能低下与2019冠状病毒病(COVID-19)严重程度增加相关。NK细胞免疫治疗可能改善免疫功能,降低感染严重度。

我们开展了首项人体研究:对住院COVID-19患者单次给予脐带血来源异基因NK细胞疗法DVX201,进行开放标签、1期剂量递增研究,剂量分别为1×10⁸、3×10⁸或9×10⁸个细胞。参与者随访28天。符合入组条件的每日泼尼松最大剂量为0.5 mg/kg(或等效剂量)。共纳入9名参与者,每个剂量组3人。8名参与者至少有1种与COVID-19严重程度增加相关的合并症,其中3人患有血液系统恶性肿瘤。输注耐受性良好,未发生治疗相关不良事件,也未发现输注相关炎症并发症。输注后外周血NK细胞总体增加,在第7天左右达到峰值。从输注到出院的中位时间为2天(范围1–13天)。2名患者(均患急性淋巴细胞白血病)因COVID-19复发再次入院。本试验证明异基因NK细胞免疫疗法作为潜在抗病毒治疗具有安全性;仍需更大规模的对照试验确定其疗效。

展开英文摘要原文

Low levels and function of natural killer (NK) cells are associated with increased coronavirus disease 2019 (COVID-19) severity. NK cell immunotherapy may improve immune function to reduce infection severity.

We conducted a first-in-human, open-label, phase 1, dose-escalating (100 10 6 , 300 10 6 , or 900 10 6 cells) study of a single dose of DVX201, a cord-blood-derived allogeneic NK cell therapy, in hospitalized patients with COVID-19. Participants were followed for 28 days. The maximum allowed steroid dose for eligibility was up to 0. 5 mg/kg prednisone (or equivalent) daily.

We enrolled nine participants, 3 per dose level. Eight participants had 1 comorbidity associated with increased COVID-19 severity, three of whom had a hematologic malignancy. Infusions were well tolerated, with no treatment-related adverse events. There was no evidence of inflammatory complications related to infusions.

Peripheral blood NK cells generally increased after infusion, peaking by day 7. The median time from infusion to discharge was 2 days (range: 1-13). Two patients (both with acute lymphoblastic leukemia) were readmitted with recurrent COVID-19. This trial demonstrates the safety of allogeneic NK cell immunotherapy as a potential antiviral. Larger controlled trials are needed to establish efficacy.

论文信息

作者
Liu WL、Kampouri E、Bui JK、Sekhon MK、Tercero A、Finlay D、Asghedom LH、Romasanta GR
单位
Fred Hutchinson Cancer Center, Seattle, WA, USA.United States
期刊
Molecular therapy. Methods & clinical development2024 Dec 12
原文标识
PubMed 39624798 · DOI 10.1016/j.omtm.2024.101361