TY - JOUR
T1 - Targeting T cells in inflammatory bowel disease
AU - Giuffrida, Paolo
AU - Di Sabatino, Antonio
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Anti-CD25 antibody
KW - Anti-CD3 antibody
KW - Anti-Cytokine
KW - Anti-NKG2D antibody
KW - Anti-TNF-α antibody
KW - Azathioprine
UR - http://www.scopus.com/inward/record.url?scp=85087170038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087170038&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2020.105040
DO - 10.1016/j.phrs.2020.105040
M3 - Review article
C2 - 32585338
AN - SCOPUS:85087170038
VL - 159
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
M1 - 105040
ER -