Research ArticleANTIMICROBIAL THERAPEUTICS

A multifunctional bispecific antibody protects against Pseudomonas aeruginosa

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Science Translational Medicine  12 Nov 2014:
Vol. 6, Issue 262, pp. 262ra155
DOI: 10.1126/scitranslmed.3009655

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Bispecific Antibodies Protect Against Pseudomonas

Multifunctional bispecific antibodies were constructed conferring three mechanisms of action against the bacterial pathogen Pseudomonas aeruginosa by targeting both the type III secretion injectisome virulence factor PcrV and the persistence factor Psl exopolysaccharide (DiGiandomenico et al.). A new multimechanistic bispecific antibody platform called BiS4αPa exhibited targeted synergistic protection against P. aeruginosa in a mouse model of lung infection compared to the parent monoclonal antibody combination. This BiS4αPa construct, now designated clinical candidate MEDI3902, was also protective in mouse models of thermal injury, bacteremia, and immunosuppression and synergistically enhanced treatment with multiple antibiotic classes. This study suggests that multifunctional bispecific antibodies may be a promising platform for targeting other antibiotic-resistant bacterial pathogens.

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