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Patients with gastrointestinal irritability after TGN1412-induced cytokine storm displayed selective expansion of gut-homing αβ and γδT cells

Authors
  • McCarthy, NE
  • Stagg, AJ
  • Price, CL
  • Mann, ER
  • Gellatly, NL
  • Al-Hassi, HO
  • Knight, SC
  • Panoskaltsis, N
Publication Date
Sep 11, 2020
Source
Spiral - Imperial College Digital Repository
Keywords
Language
English
License
Unknown

Abstract

Following infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of 'gut-homing' integrin β7 on peripheral blood αβT cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2+ γδT cells in the circulation which declined over a 2-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal symptoms were associated with dysregulation of the 'gut-homing' pool of blood αβ and γδT cells, induced directly by the antibody and/or arising from the subsequent cytokine storm.

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