Open AccessA novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond
Author(s) -
Shapira Shiran,
Ben Shimon Marina,
HayLevi Mori,
Shenberg Gil,
Choshen Guy,
Ban Lian,
Tepper Michael,
Kazanov Dina,
Seni Jonathan,
LevAri Shahar,
Peer Michael,
Boubas Dimitrios,
Stebbing Justin,
Tsiodras Sotirios,
Arber Nadir
Publication year - 2022
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202215997
Subject(s) - tel aviv , health promotion , center (category theory) , cancer prevention , promotion (chess) , library science , public health , medicine , cancer , political science , law , nursing , chemistry , politics , computer science , crystallography
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.