Antibody‐antibiotic conjugates: a new platform for treatment of serious bacterial infections

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long‐term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. We have shown that intracellular S. aureus in mice can establish infection even in the presence of vancomycin, and we have developed a novel therapeutic that effectively kills intracellular S. aureus . This antibody‐antibiotic conjugate consists of an anti‐ S. aureus antibody that recognizes a highly expressed epitope on wall teichoic acid, conjugated to a potent antibiotic that is activated only after its release from the antibody in the proteolytic environment of the phagolysosome. The antibody‐antibiotic conjugate is superior to vancomycin for treatment of bacteremia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections. This paradigm may have implications for treatment of other bacterial infections. Support or Funding Information This work was funded by Genentech, Inc.