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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere15997
JournalEMBO Molecular Medicine
Volume14
Issue number9
DOIs
StatePublished - 7 Sep 2022

Keywords

  • CD24
  • COVID-19
  • EXO-CD24
  • cytokine storm
  • exosomes

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