当前位置: X-MOL 学术EMBO Mol. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A novel platform for attenuating immune hyperactivity using EXO-CD24 in COVID-19 and beyond
EMBO Molecular Medicine ( IF 11.1 ) Pub Date : 2022-07-13 , DOI: 10.15252/emmm.202215997
Shiran Shapira 1, 2 , Marina Ben Shimon 1 , Mori Hay-Levi 1 , Gil Shenberg 1 , Guy Choshen 3 , Lian Bannon 4 , Michael Tepper 1 , Dina Kazanov 1 , Jonathan Seni 1, 2 , Shahar Lev-Ari 1, 2 , Michael Peer 5 , Dimitrios Boubas 6 , Justin Stebbing 7 , Sotirios Tsiodras 6 , Nadir Arber 1, 2
Affiliation  

A small but significant proportion of COVID-19 patients develop life-threatening cytokine storm. We have developed a new anti-inflammatory drug, EXO-CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF-kB pathway and the production of cytokines/chemokines. EXO-CD24 discriminates damage-from pathogen-associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO-CD24 was produced and purified from CD24-expressing 293-TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO-CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo. In a phase Ib/IIa study, 35 patients with moderate–high severity COVID-19 were recruited and given escalating doses, 108–1010, of EXO-CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443–575 days. EXO-CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO-CD24 may be a treatment strategy to suppress the hyper-inflammatory response in the lungs of COVID-19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm.

中文翻译:

在 COVID-19 及以后使用 EXO-CD24 减轻免疫机能亢进的新平台

一小部分但很大比例的 COVID-19 患者会出现危及生命的细胞因子风暴。我们开发了一种新的抗炎药 EXO-CD24,它结合了免疫检查点 (CD24) 和递送平台(外泌体)。CD24 抑制 NF-kB 通路和细胞因子/趋化因子的产生。EXO-CD24 可区分病原体相关分子模式(DAMP 和 PAMP)造成的损害,因此不会干扰病毒清除。EXO-CD24 是从表达 CD24 的 293-TREx™ 细胞中产生和纯化的。还产生了展示鼠 CD24 (mCD24) 的外泌体。在体外体内对 EXO-CD24/mCD24 的安全性和有效性进行了表征和检查. 在一项 Ib/IIa 期研究中,招募了 35 名中重度 COVID-19 患者,并通过吸入 QD 的方式给予递增剂量的 EXO-CD24,剂量为 10 8 –10 10,持续 5 天。长达 443-575 天未观察到与药物相关的不良事件。EXO-CD24 有效降低炎症标志物和细胞因子/趋化因子,尽管需要进行随机研究。EXO-CD24可能是一种抑制COVID-19患者肺部过度炎症反应的治疗策略,并进一步作为其他以细胞因子风暴为特征的肺部和全身性疾病的治疗平台。
更新日期:2022-07-13
down
wechat
bug