Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 4, Pages 1155-1160Publisher
SPRINGER
DOI: 10.1007/s00262-020-02702-9
Keywords
Cytokine storm; Cytokine release syndrome; TGN1412; Anemia of inflammation; Dysgranulopoiesis
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Funding
- North West London Hospitals NHS Trust
- Cancer Research UK
- Northwick Park Hospital Leukemia Research Trust Fund
- BBSRC [BBS/E/F/000PR10353, BBS/E/F/000PR10356, BBS/E/F/000PR10355] Funding Source: UKRI
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TGN1412, a superagonist monoclonal antibody targeting CD28, caused cytokine storm in healthy volunteers, leading to anemia and granulocytic dysplasia which resolved over several months. The study provides insights into the changes in myelopoiesis and natural resolution in young healthy individuals following acute inflammation and cytokine storm.
TGN1412, a superagonist monoclonal antibody targeting CD28, caused cytokine storm in six healthy volunteers in a first-in-man study in 2006. Despite clinical improvement and termination of the cytokine release syndrome within days, anemia persisted in all patients with hemoglobin reaching baseline levels as much as 6 months later. Granulocytic dysplasia continued for 20 days in association with increased expression of CD69 and IL-4, but reduced IL-10; with resolution, this profile reversed to higher IL-10 expression and counter-balanced circannual cycling of IL-4 and IL-10 thereafter over 7 months. Along with immune cell subset and cytokine correlates monitored over 2 years, these observations offer unique insights into the expected changes in myelopoiesis and natural resolution in otherwise healthy young individuals in response to acute inflammation and cytokine storm in the absence of concomitant infection or comorbidity.
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