A chimeric anti-TNFalpha monoclonal antibody (cA2) in vivo removes TNFalpha-producing cells in Crohn's disease.

ABSTRACT

Tumor necrosis factor alpha (TNFalpha) has been described as a citokine involved in gastrointestinal mucosal inflammation in Crohn's disease. A single infusion of the chimeric mouse/human monoclonal antibody cA2 anti-TNFalpha has been established as a new therapeutical procedure. The aim of these study was to determine the effect of the monoclonal antibody cA2 on lymphocyte and monocyte TNFalpha-producing cells. Initially the patient, with severe Crohn's disease (Crohn's disease activity index CDAI > 350), presented a higher number of peripheral blood TNFalpha-producing cells than healthy controls. The patient received two cA2 treatments throughout one year due the severe activity of the disease. Before treatment the patient had a large number of TNFalpha producer cells. A dramatic reduction in lymphocyte and monocyte TNFalpha producing cells, together a clinical remission (CDAI < 150), was shown after the treatments. Four months after the first cA2 treatment, the patient had a clinical response associated with an important increment of TNFalpha-producing cells that extended increasing until the second cA2 treatment was averaged. These results suggest that the clinical activity of the Crohn's disease correlates with peripheral TNFalpha-expressing cells. The cA2 antibody, as well as of neutralize soluble TNFalpha, also removes TNFalpha-producer cells, which may collaborate with the anti-TNFalpha activity of the antibody treatment.