2018
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Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics
Abstract: First infusion reactions along with severe anaphylactic responses can occur as a result of systemic administration of therapeutic antibodies. The underlying mechanisms by which monoclonal antibodies induce cytokine release syndrome (CRS) can involve direct agonistic effects via the drug target, or a combination of target-engagement along with innate receptor interactions. Despite the wide variety of pathways and cells that can play a role in CRS, many currently used assays are devoid of one or more components … Show more
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“…In a second assay, a cytokine release profile of CD28xVISTA pH-sens BS2 was generated in an ex vivo platform that mimics human blood circulation for a more accurate CRS prediction (Figure 7A; (20)). Ex vivo cytokine release in fresh human whole blood from 6 healthy donors by CD28xVISTA pH-sens BS2 was compared to CD28 ADI xVISTA pH-sens BS2 and R-5678 at concentrations of 1, 10 and 100 μg/ml (mirroring realistic clinical plasma levels) and the controls anti-CD28 (ANC.28.1; 1 μg/ml), Alemtuzumab (3 μg/ml) or Cetuximab (250 μg/ml).…”
Section: Resultsmentioning
confidence: 99%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).
Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.
The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).
Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…In a second assay, a cytokine release profile of CD28xVISTA pH-sens BS2 was generated in an ex vivo platform that mimics human blood circulation for a more accurate CRS prediction (Figure 7A; (20)). Ex vivo cytokine release in fresh human whole blood from 6 healthy donors by CD28xVISTA pH-sens BS2 was compared to CD28 ADI xVISTA pH-sens BS2 and R-5678 at concentrations of 1, 10 and 100 μg/ml (mirroring realistic clinical plasma levels) and the controls anti-CD28 (ANC.28.1; 1 μg/ml), Alemtuzumab (3 μg/ml) or Cetuximab (250 μg/ml).…”
Section: Resultsmentioning
confidence: 99%
“…Cytokine release profile of CD28xVISTA pH-sens BS2 in an ex vivo system that mimics human blood circulation Ex vivo cytokine release in human whole blood from 6 healthy donors by CD28xVISTA pH-sens BS2, CD28 ADI xVISTA pH-sens BS2 (both with pH selective VISTA binding), and R-5678 was tested by Immuneed, AB using their ID.Flow circulating blood platform (20) with the controls anti-CD28 (ANC.28.1; 1 μg/ml), Alemtuzumab (3 μg/ml) or Cetuximab (250 μg/ml). Fresh whole blood was taken from healthy volunteers and a low amount of soluble heparin (allowing for analysis of drugrelated effects on complement or coagulation cascade systems) was added.…”
Section: Assessment Of Cd28xvista Ph-sens Bs2 In An In Vitro Cytokine...mentioning
confidence: 99%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).
Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.
The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).
Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…Fresh whole blood was taken from three healthy volunteers and a low amount of soluble heparin was added. The blood was immediately transferred into closed loops followed by administration of the test items, and set to rotate (to mimic the blood circulation) at 37°C to prevent clotting ( 50 ). For each donor the same test conditions were analyzed: fresh blood was used for hematology measurements directly after blood collection (baseline value) and then each test condition was sampled at 4, 8, and 24 hours after the addition of the test items, with 10 mmol/L EDTA added to each sample to stop the reactions at sampling time points.…”
Section: Methodsmentioning
confidence: 99%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).
Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.
The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).
Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…Blood loop experiments were performed as described previously. [ 21 ] In brief, whole blood samples were collected from healthy blood donors, and the blood was added to surface heparinized PVC loops together with the peptide/antibody of interest in the presence of brefeldin‐A. The blood loops were attached to a circulating wheel to allow the blood to be in motion and prevent coagulation.…”
Section: Methodsmentioning
confidence: 99%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).
Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.
The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).
Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
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