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评估新型冠状病毒肺炎中自然杀伤细胞安全性的I期RELEASE临床试验。

The phase I RELEASE clinical trial to evaluate the safety of NK cells in COVID-19.

作者信息

Hernández-Blanco Clara, Al-Akioui-Sanz Karima, Herrera Lara, Aguirre-Portolés Cristina, Lozano-Ojalvo Daniel, Pérez-Rodriguez Leticia, Cano-Ochando Jordi, Guerra-García Pilar, Martín-Quirós Alejandro, Vicario José Luis, Santos Silvia, Pérez-Vaquero Miguel Ángel, Vesga Miguel Ángel, Borobia Alberto M, Carcas Antonio J, Balas Antonio, Moreno Miguel Ángel, Pérez de Diego Rebeca, Gasior Mercedes, Soria Bernat, Eguizabal Cristina, Pérez-Martínez Antonio

机构信息

Internal Medicine Department, University Hospital La Paz, Madrid, Spain.

Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.

出版信息

iScience. 2024 Dec 27;28(2):111698. doi: 10.1016/j.isci.2024.111698. eCollection 2025 Feb 21.

DOI:
10.1016/j.isci.2024.111698
PMID:39877904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11772958/
Abstract

The severity of COVID 19 symptoms has a direct correlation with lymphopenia, affecting natural killer (NK) cells. SARS-CoV-2 specific "memory" NK cells obtained from convalescent donors can be used as cell immunotherapy. In 2022 a phase I, dose-escalation, single center clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD3/CD56 NK cells against moderate/severe cases of COVID-19 (NCT04578210). Six participants with pneumonia and/or lymphopenia were infused. Four patients received a single-dose infusion of NK cells of 1×10/kg, and the following two patients a dose of 2×10/kg of NK cells. All participants' clinical status and inflammation markers were monitored. No serious adverse events were reported after infusion. Exploratory outcomes included the donor chimerism, NK-cell immunophenotype evolution, and immune lymphocyte reconstitution. This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using NK from COVID-19 convalescent donors is feasible and safe.

摘要

新冠病毒 19 症状的严重程度与淋巴细胞减少直接相关,影响自然杀伤(NK)细胞。从康复供体获得的新冠病毒 2 特异性“记忆”NK 细胞可用于细胞免疫治疗。2022 年进行了一项 I 期、剂量递增、单中心临床试验,以评估输注 CD3/CD56 NK 细胞治疗中度/重度新冠病毒 19 病例(NCT04578210)的安全性和可行性。六名患有肺炎和/或淋巴细胞减少的参与者接受了输注。四名患者接受了 1×10/kg 的 NK 细胞单剂量输注,随后两名患者接受了 2×10/kg 的 NK 细胞剂量输注。监测了所有参与者的临床状况和炎症标志物。输注后未报告严重不良事件。探索性结果包括供体嵌合现象、NK 细胞免疫表型演变和免疫淋巴细胞重建。本研究提供了初步证据,支持使用来自新冠病毒 19 康复供体的 NK 细胞治疗中度/重度症状的新冠病毒 19 患者是可行且安全的这一观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/11772958/a2f2b9ecec52/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/11772958/0c396c958aea/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/11772958/a2f2b9ecec52/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/11772958/0c396c958aea/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/11772958/a2f2b9ecec52/gr1.jpg

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本文引用的文献

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Off-the-shelf allogeneic natural killer cells for the treatment of COVID-19.用于治疗新冠肺炎的现成同种异体自然杀伤细胞。
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Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).二期随机多中心研究结果,评估输注记忆 T 细胞作为新型严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)肺炎和/或淋巴细胞减少症的过继疗法的安全性和有效性(RELEASE NCT04578210)。
Cytotherapy. 2024 Jan;26(1):25-35. doi: 10.1016/j.jcyt.2023.10.002. Epub 2023 Oct 29.
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Trials. 2021 Oct 2;22(1):674. doi: 10.1186/s13063-021-05625-7.
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