Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies

We examined the ability of a bispecific mAb reagent, consisting of a mAb sp ecific for the primate erythrocyte complement receptor cross-linked with an anti-bacterial mAb, to target bacteria in the bloodstream in an acute infu sion model in monkeys. In vitro studies demonstrated a variable level of co mplement-mediated binding (immune adherence) of Pseudomonas aeruginosa (str ain PAO1) to primate E in serum. In vivo experiments in animals depleted of complement revealed that binding of bacteria to E was <1% before administr ation of the bispecific reagent, but within 5 min of its infusion, > 99% of the bacteria bound to E. In complement-replete monkeys, a variable fractio n of infused bacteria bound to E. This finding may have significant implica tions in the interpretation of animal models and in the understanding of ba cteremias in humans. Treatment of these complement-replete monkeys with the bispecific reagent led to > 99% binding of bacteria to E. Twenty-four-hour survival studies were conducted; several clinical parameters, including th e degree of lung damage, cytokine levels, and liver enzymes in the circulat ion, indicate that the bispecific mAb reagent provides a degree of protecti on against the bacterial challenge.