Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection

Bellio, Michael; Bennett, Cassie; Arango, Alissa; Khan, Aisha; Xu, Xiumin; Barrera, Cesar; Friedewald, Vincent E.; Mitrani, Maria Ines

doi:10.1016/j.bbiosy.2021.100031

Cited by 11 publications

(15 citation statements)

References 50 publications

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“…Given their anti-inflammatory potential, a proof-of-concept clinical trial was performed in 8 patients with mild-to-moderate COVID-19 who were hospitalized but not intubated (NCT04384445 & NCT04657406) and treated with Zofrin (a type of exosomal vesicle). Results showed that Zofrin treatment resulted in symptomatic resolution by Day 30 with no indication of disease progression as verified by imaging and trending inflammatory markers where both improved and decreased, respectively [114]. No adverse events were observed.…”

Section: Exosomal Therapymentioning

confidence: 77%

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients

et al. 2023

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Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence—including Allocetra, monoclonal antibodies (Tixagevimab–Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus’s rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.

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Section: Exosomal Therapymentioning

confidence: 77%

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients

et al. 2023

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“…Zofin, an acAF biologic containing AF-EVs, is hypothesized to reduce systemic inflammation and is currently being tested in the clinic to treat SARS-COV2 infection and post SARS-COV2 long hauler syndrome [NCT05228899]. Zofin has already been tested on a subset of COVID-19 patients and has shown promising clinical results such as decreases in pro-inflammatory cytokine levels ( 8 , 9 , 45 ). Here we show the potential of acAF to decrease pro-inflammatory cytokine release in stimulated PBMCs, specifically GM-CSF, IL-13, and IFNγ.…”

Section: Discussionmentioning

confidence: 99%

“…AF-derived EVs (AF-EVs) can regulate angiogenesis and are capable of altering lung tissue structure ( 6 , 7 ). Additionally, AF-derived treatments have recently entered the clinic as a novel therapeutic for the treatment of COVID-19 long haulers and COVID-19 induced acute respiratory distress syndrome and inflammation ( 8 , 9 ). However, the extracellular components of AF have not been extensively studied to understand their biological functions, systemic effects, or therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Human amniotic fluid derived extracellular vesicles attenuate T cell immune response

et al. 2022

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IntroductionExtracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model. However, the effects of acellular amniotic fluid (acAF) or AF-EVs on the T-Cell immune response have not been explored.MethodsIn this study, we investigated the effects of acAF and AF-EVs on the T cell immune response in an in vitro cell culture model. Peripheral Blood Mononuclear Cells (PBMCs) were stimulated with Phytohemagglutinin (PHA) to induce the immune response and were subsequently treated with either serum-free media (vehicle), acAF, or concentrated AF-EVs. ResultsBoth acAF and AF-EV treatment suppressed PHA-induced T cell proliferation and PHA-induced T cell activation; however, treatment with concentrated AF-EVs had a greater effect. Additionally, both acAF and AF-EVs reduced PBMC pro-inflammatory cytokine release. AF-EVs were found to be taken up by both CD4+ and CD8+ effector T cell subsets.ConclusionOverall, this data demonstrates that AF-EVs have a robust immunomodulatory effect on T cells and suggests AF-EVs could be used as an immunotherapeutic tool.

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“…Another group performed similar studies in COVID-19 patients with mild-moderate symptoms, also by injecting cfAF intravenously. The authors reported a significant reduction in inflammatory biomarker levels and other secondary markers of COVID-19 severity [ 84 ]. In another case study, three severely ill COVID-19 patients were treated with cAF and showed rapid and significant improvements in sequential organ failure assessment (SOFA) scores, ICU status, and respiratory function following treatment [ 88 ].…”

Section: Current Clinical Studies/applications Using Cell-free Amniot...mentioning

confidence: 99%

Cell-Free Amniotic Fluid and Regenerative Medicine: Current Applications and Future Opportunities

et al. 2022

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Amniotic fluid (AF) provides critical biological and physical support for the developing fetus. While AF is an excellent source of progenitor cells with regenerative properties, recent investigations indicate that cell-free AF (cfAF), which consists of its soluble components and extracellular vesicles, can also stimulate regenerative and reparative activities. This review summarizes published fundamental, translational, and clinical investigations into the biological activity and potential use of cfAF as a therapeutic agent. Recurring themes emerge from these studies, which indicate that cfAF can confer immunomodulatory, anti-inflammatory, and pro-growth characteristics to the target cells/tissue with which they come into contact. Another common observation is that cfAF seems to promote a return of cells/tissue to a homeostatic resting state when applied to a model of cell stress or disease. The precise mechanisms through which these effects are mediated have not been entirely defined, but it is clear that cfAF can safely and effectively treat cutaneous wounds and perhaps orthopedic degenerative conditions. Additional applications are currently being investigated, but require further study to dissect the fundamental mechanisms through which its regenerative effects are mediated. By doing so, rational design can be used to fully unlock its potential in the biotechnology lab and in the clinic.

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Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection

Cited by 11 publications

References 50 publications

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients

Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients

Human amniotic fluid derived extracellular vesicles attenuate T cell immune response

Cell-Free Amniotic Fluid and Regenerative Medicine: Current Applications and Future Opportunities

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