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, 10 8 -10 10 , 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.
Keywords: CD24; COVID-19; EXO-CD24; cytokine storm; exosomes.
【저자키워드】 COVID-19, Cytokine storm, CD24, EXO-CD24, exosomes., 【초록키워드】 Treatment, Exosome, Efficacy, severity, lung, Exosomes, cytokine, in vitro, viral clearance, immune, cells, therapeutic, adverse event, Patient, Inflammatory marker, in vivo, platform, Combination, systemic disease, PAMPs, COVID-19 patient, pathogen-associated molecular pattern, hyper-inflammatory response, life-threatening, randomized study, doses, anti-inflammatory drug, NF-kB pathway, murine, produced, develop, examined, proportion, recruited, inhibit, required, reduced, characterized, interfere, suppress, displaying, purified, 【제목키워드】 immune, platform, hyperactivity,