Myelopoiesis of acute inflammation: lessons from TGN1412-induced cytokine storm

Cancer Immunol Immunother. 2021 Apr;70(4):1155-1160. doi: 10.1007/s00262-020-02702-9. Epub 2020 Aug 30.

Abstract

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.

Keywords: Anemia of inflammation; Cytokine release syndrome; Cytokine storm; Dysgranulopoiesis; TGN1412.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • CD28 Antigens / immunology*
  • Cytokine Release Syndrome / chemically induced
  • Cytokine Release Syndrome / immunology*
  • Cytokines / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology*
  • Leukocytes, Mononuclear / immunology*
  • Male
  • Myelopoiesis / drug effects
  • Myelopoiesis / immunology*
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • CD28 Antigens
  • Cytokines
  • TGN-1412