新型冠状病毒肺炎所致急性肺炎患者输注体外扩增的异体自然杀伤细胞的安全性和可行性研究
Safety and feasibility study of ex vivo expanded allogeneic-NK cells infusion in patients with acute pneumonia caused by COVID-19.
作者信息
Ahmadvand Mohammad, Barough Mahdieh Shokrollahi, Hashemi Zahra Sadat, Sanati Hassan, Abbasvandi Fereshteh, Yunesian Masud, Majidzadeh-A Keivan, Makarem Jalil, Aghayan Hamid Reza, Abedini Atefeh, Ghavamzadeh Ardeshir, Forooshani Ramin Sarrami
机构信息
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran, Iran.
出版信息
Pilot Feasibility Stud. 2023 Aug 4;9(1):137. doi: 10.1186/s40814-023-01355-6.
BACKGROUND
NK cells are the most active innate immune cells in antiviral immunity, which are impaired by SARS-COV2 infection. Infusion of allogeneic NK cells might be a complementary treatment to boost immune system function in COVID-19 patients. In this project, we focused on COVID-19 patients with low inspiratory capacity (LIC). This project aims to evaluate the feasibility and safety of allogeneic NK cell infusion as an intervention for respiratory viral disease.
METHODS
A non-blind two arms pilot study was designed and conducted after signing the consent form. Ten matched patients, in terms of vital signs and clinical features, were enrolled in the control and intervention groups. Approximately 2 × 10^6 cells/kg of NK cells were prepared under GCP (good clinical practice) conditions for each patient in the intervention group. The control group was under the same conditions and drug regimen except for the treatment with the prepared cells. Then, infused intravenously during 20 min in the ICU ward of Masih Daneshvari Hospital. The clinical signs, serological parameters, and CTCAE (Common Terminology Criteria for Adverse Events) were recorded for safety evaluation and the feasibility of project management were evaluated via designed checklist based on CONSORT.
RESULTS
There were no symptoms of anaphylaxis, hypersensitivity, significant changes in blood pressure, cardiovascular complications, and fever from injection time up to 48 h after cell infusion. The mean hospitalization period in the control and intervention groups was 10 and 8 days, respectively. The blood O2 saturation level was raised after cell infusion, and a significantly lower mean level of inflammatory enzymes was observed in the intervention group following discharge compared to the control group (p < 0.05). The inflammatory parameters differences at the discharge date in cell therapy group were highly negative.
CONCLUSION
Intravenous infusion of ex vivo-expanded allogeneic NK cells was safe and feasible. However, the efficacy of this approach to reducing the severity of disease in COVID-19 patients with LIC could not be determined.
TRIAL REGISTRATION
Name of the registry: NKCTC. IRCT20200621047859N2. December 29, 2020. URL of trial registry record: https://www.irct.ir/trial/49382.
背景
自然杀伤细胞（NK细胞）是抗病毒免疫中最活跃的先天性免疫细胞，其功能会因感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）而受损。输注异体NK细胞可能是增强新型冠状病毒肺炎（COVID-19）患者免疫系统功能的一种补充治疗方法。在本项目中，我们聚焦于吸气能力低（LIC）的COVID-19患者。本项目旨在评估异体NK细胞输注作为呼吸道病毒疾病干预措施的可行性和安全性。
方法
设计并开展了一项非盲双臂试点研究，研究前签署了知情同意书。根据生命体征和临床特征匹配的10名患者被纳入对照组和干预组。在药物临床试验质量管理规范（GCP）条件下，为干预组的每位患者制备约2×10^6个细胞/千克的NK细胞。对照组除不接受所制备细胞的治疗外，处于相同条件并采用相同药物治疗方案。然后，在马西·达内什瓦里医院的重症监护病房（ICU）病房于20分钟内静脉输注。记录临床体征、血清学参数和不良事件通用术语标准（CTCAE）以进行安全性评估，并通过基于CONSORT设计的检查表评估项目管理的可行性。
结果
从注射时到细胞输注后48小时，未出现过敏反应、超敏反应、血压显著变化、心血管并发症和发热症状。对照组和干预组的平均住院时间分别为10天和8天。细胞输注后血氧饱和度水平升高，与对照组相比，干预组出院后炎症酶平均水平显著降低（p<0.05）。细胞治疗组出院时的炎症参数差异为高度阴性。
结论
静脉输注体外扩增的异体NK细胞是安全可行的。然而，这种方法降低LIC的COVID-19患者疾病严重程度的疗效尚无法确定。
试验注册
注册机构名称：NKCTC。IRCT20200621047859N2。2020年12月29日。试验注册记录的网址：https://www.irct.ir/trial/49382。
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