Life-saving immunotherapy with cross-reactive monoclonal antibodies against endotoxin: a critical evaluation of experimental and clinical studies.

In this paper clinical and experimental studies are reviewed for evidence that monoclonal antibodies (MoAbs), directed against common epitopes in the core glycolipid region of lipopolysaccharide (LPS) of gram-negative bacteria, protect against the lethal effect of bacteremia of serologically unrelated gram-negative bacteria. Only those experimental studies that included control MoAbs and excluded the possibility of survival due to endotoxin tolerance, provided evidence for the protective efficacy of cross-reactive MoAbs. Two recently performed clinical trials evaluating the protective value of the MoAbs HA-1A and E5 showed beneficial effects (enhanced survival) by each MoAb in different subgroups of patients with proven gram-negative bacterial infections. It is concluded that immunotherapy by MoAbs is a promising new tool in the treatment of gram-negative bacterial septic shock. However, the pathophysiological mechanism of protection remains to be elucidated and the group of patients which may benefit most remains to be defined more clearly. Therefore, further experimental and clinical studies are warranted.