Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients
Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2523 |
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| author | Orr Green Gil Shenberg Roni Baruch Lihi Argaman Talya Levin Ian Michelson Ruthy Hadary Boris Isakovich Miri Golos Reut Schwartz Ronan MacLoughlin Nimrod Adi Nadir Arber Shiran Shapira |
| author_facet | Orr Green Gil Shenberg Roni Baruch Lihi Argaman Talya Levin Ian Michelson Ruthy Hadary Boris Isakovich Miri Golos Reut Schwartz Ronan MacLoughlin Nimrod Adi Nadir Arber Shiran Shapira |
| author_sort | Orr Green |
| collection | DOAJ |
| description | Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings. |
| first_indexed | 2024-03-10T23:00:04Z |
| format | Article |
| id | doaj.art-279f02338c0d4c76b4e8338848d39cc4 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:04Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-279f02338c0d4c76b4e8338848d39cc42023-11-19T09:42:31ZengMDPI AGBiomedicines2227-90592023-09-01119252310.3390/biomedicines11092523Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS PatientsOrr Green0Gil Shenberg1Roni Baruch2Lihi Argaman3Talya Levin4Ian Michelson5Ruthy Hadary6Boris Isakovich7Miri Golos8Reut Schwartz9Ronan MacLoughlin10Nimrod Adi11Nadir Arber12Shiran Shapira13Health Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelDepartment of Internal Medicine C, Meir Medical Center, Kefar-Saba 4428164, IsraelIntensive Care Unit, Hillel Yaffe Medical Center, Hadera 3820302, IsraelCarmel Medical Center, Haifa 3436212, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, IsraelSchool of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, D02 YN77 Dublin, IrelandSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelHealth Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelRationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings.https://www.mdpi.com/2227-9059/11/9/2523exosomesCD24EXO-CD24acute respiratory distress syndromeARDSCOVID-19 |
| spellingShingle | Orr Green Gil Shenberg Roni Baruch Lihi Argaman Talya Levin Ian Michelson Ruthy Hadary Boris Isakovich Miri Golos Reut Schwartz Ronan MacLoughlin Nimrod Adi Nadir Arber Shiran Shapira Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients Biomedicines exosomes CD24 EXO-CD24 acute respiratory distress syndrome ARDS COVID-19 |
| title | Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients |
| title_full | Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients |
| title_fullStr | Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients |
| title_full_unstemmed | Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients |
| title_short | Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients |
| title_sort | inhaled exosomes genetically manipulated to overexpress cd24 exo cd24 as a compassionate use in severe ards patients |
| topic | exosomes CD24 EXO-CD24 acute respiratory distress syndrome ARDS COVID-19 |
| url | https://www.mdpi.com/2227-9059/11/9/2523 |
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