A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond
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 c...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-07-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202215997 |
| _version_ | 1826990679790714880 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shiran Shapira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:25:21Z |
| format | Article |
| id | doaj.art-e8cb646be73748bdab517e8146718ff6 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T08:25:04Z |
| publishDate | 2022-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-e8cb646be73748bdab517e8146718ff62024-11-03T12:39:41ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-07-0114911710.15252/emmm.202215997A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyondShiran Shapira0Marina Ben Shimon1Mori Hay‐Levi2Gil Shenberg3Guy Choshen4Lian Bannon5Michael Tepper6Dina Kazanov7Jonathan Seni8Shahar Lev‐Ari9Michael Peer10Dimitrios Boubas11Justin Stebbing12Sotirios Tsiodras13Nadir Arber14The Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterDepartment of Internal Medicine H, Tel Aviv Sourasky Medical CenterDepartment of Internal Medicine F, Tel Aviv Sourasky Medical CenterThe Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterThe Health Promotion Center and Integrated Cancer Prevention CenterDepartment of Thoracic Surgery, Tel Aviv Sourasky Medical Center4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical SchoolDepartment of Surgery and Cancer, Imperial College4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical SchoolThe Health Promotion Center and Integrated Cancer Prevention CenterAbstract 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.https://doi.org/10.15252/emmm.202215997CD24COVID‐19cytokine stormexosomesEXO‐CD24 |
| spellingShingle | 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 A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond EMBO Molecular Medicine CD24 COVID‐19 cytokine storm exosomes EXO‐CD24 |
| title | A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond |
| title_full | A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond |
| title_fullStr | A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond |
| title_full_unstemmed | A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond |
| title_short | A novel platform for attenuating immune hyperactivity using EXO‐CD24 in COVID‐19 and beyond |
| title_sort | novel platform for attenuating immune hyperactivity using exo cd24 in covid 19 and beyond |
| topic | CD24 COVID‐19 cytokine storm exosomes EXO‐CD24 |
| url | https://doi.org/10.15252/emmm.202215997 |
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