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A novel platform for attenuating immune hyperactivity using EXO-CD24 in COVID-19 and beyond.
Shapira, Shiran; Ben Shimon, Marina; Hay-Levi, Mori; Shenberg, Gil; Choshen, Guy; Bannon, Lian; Tepper, Michael; Kazanov, Dina; Seni, Jonathan; Lev-Ari, Shahar; Peer, Michael; Boubas, Dimitrios; Stebbing, Justin; Tsiodras, Sotirios; Arber, Nadir.
  • Shapira S; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Ben Shimon M; Department of Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Hay-Levi M; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Shenberg G; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Choshen G; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Bannon L; Department of Internal Medicine H, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Tepper M; Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Kazanov D; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Seni J; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Lev-Ari S; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Peer M; Department of Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Boubas D; The Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv, Israel.
  • Stebbing J; Department of Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Tsiodras S; Department of Thoracic Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • Arber N; 4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
EMBO Mol Med ; 14(9): e15997, 2022 09 07.
Article in English | MEDLINE | ID: covidwho-1918175
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Exosomes / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2022 Document Type: Article Affiliation country: Emmm.202215997

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Exosomes / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2022 Document Type: Article Affiliation country: Emmm.202215997