A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond

Autor: Shiran Shapira, Marina Ben Shimon, Mori Hay‐Levi, Gil Shenberg, Guy Choshen, Lian Bannon, Michael Tepper, Dina Kazanov, Jonathan Seni, Shahar Lev‐Ari, Michael Peer, Dimitrios Boubas, Justin Stebbing, Sotirios Tsiodras, Nadir Arber
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 14, Iss 9, Pp 1-17 (2022)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202215997
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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