Antibodies Anti Integrin

A therapeutic approach in UC could be the inhibition of migration of leukocytes into the inflamed intestine by blocking cellular adhesion molecules. The a4P7 integrin is primarily involved in the recruitment of leukocytes in the gut; it is present on the cell surface of a small population of circulating T lymphocytes. Its major ligand is mucosal-addressin-cell adhesion molecule 1, selectively expressed on the endothelium of the intestinal vasculature especially in the inflamed bowel. MLN02 is a monoclonal antibody that specifically recognises the a4P7 heterodimer.

Its efficacy in UC was recently assessed in a multi-centre double-blind placebo-controlled trial [73]. A clinical improvement was observed in 66% of patients on 0.5 mg/kg/day of MLN02, in 53% on 2 mg/kg/day of MLN02 and in 33% on placebo. The role of MLN02 in clinical practice needs to be carefully evaluated to define its safety profile. In fact, natalizumab, a similar drug that interrupts leukocyte homing through the blockade of the a4p1 integrin, reduced immune surveillance in the brain with subsequent reactivation of the JC virus. This led to progressive multifocal leuko-encephalopathy, invariably fatal, in three patients and the drug was withdrawn from the market [74].

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