Inhibition of in vivo neutrophil transmigration by a novel humanized anti-CD11/CD18 monoclonal antibody

Leukocyte adhesion receptors, including the beta (-)-integrin (CD11/CD18) f amily, play an important role in inflammation via their regulatory effects on leukocyte adhesion, transmigration, and function. A randomized, placebo- controlled, double-blind study was conducted in healthy volunteers to evalu ate the in vivo effects of a humanized anti-CD11/CD18 monoclonal antibody, Hu23F2G, on leukocyte activation and transmigration. Neutrophil migration t o a site of cutaneous inflammation in vivo, as measured by the skin chamber technique, was significantly reduced in subjects 24 hours after Hu23F2G ad ministration. At 96 hours, neutrophil migration was not significantly diffe rent in subjects who received Hu23F2G or placebo. In contrast, delayed-type hypersensitivity (DTH) testing, which involves activation and migration of T lymphocytes and macrophages, was unaffected by the Hu23F2G treatment. Th ese responses to Hu23F2G in vivo are similar to the clinical phenotype of l eukocyte adhesion deficiency (LAD) type 1, a congenital disorder of CD18 de ficiency. The in vivo properties of Hu23F2G suggest therapeutic potential f or use in the treatment of acute non-infectious inflammatory disorders medi ated predominantly by neutrophils.