Targeting T cells in inflammatory bowel disease

Paolo Giuffrida, Antonio Di Sabatino

Research output: Contribution to journalReview articlepeer-review

Abstract

T cells play a pivotal role in the immune response underlying inflammatory bowel disease (IBD) pathogenesis. On this basis, over the past 25 years several drugs have assessed to target T cells in IBD patients. Amongst anti-CD3 antibodies, visilizumab and foralumab did not show clinical efficacy in ulcerative colitis (UC) and Crohn's disease (CD) patients, respectively, whereas otelixizumab has been tested in vitro only. The anti-CD4 BF-5 and cM-T412, and the anti-CD25 basiliximab and daclizumab were not effective in CD and UC patients, respectively. The anti-NKG2D antibody NNC0142−0002 showed clinical benefit in CD patients, in particular in biologic naïve ones, in a randomized, double-blind, parallel-group, placebo-controlled trial. The anti-CD40L M90 and the GSK1349571A blocking calcium release-activated calcium (CRAC) channels, which are involved in the T cell activation and proliferation, were tested only in ex vivo/in vitro experiments. Apart from ustekinumab, all the other drugs targeting T cell-derived cytokines failed. The reinduction of lamina propria T cell apoptosis is a mechanism to modulate T cell survival exploited by cyclosporin A, azathioprine and anti-tumor necrosis factor-α agents, such as infliximab, adalimumab and golimumab. In this article, we review the drugs targeting T cells via surface receptors, via T cell-derived cytokines, via CRAC channels or by inducing apoptosis.

Original languageEnglish
Article number105040
JournalPharmacological Research
Volume159
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Anti-CD25 antibody
  • Anti-CD3 antibody
  • Anti-Cytokine
  • Anti-NKG2D antibody
  • Anti-TNF-α antibody
  • Azathioprine

ASJC Scopus subject areas

  • Pharmacology

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