Shaking Hands with Streptococcal Antibody-Degrading Enzymes for Clinical Use (Review)

Abstract

Antibody-degrading enzymes are one among crucial virulence factors of pathogenic bacteria and parasites for they help the inhabitant evade the attacks of the host immune system. IdeS and EndoS are two such well-characterised enzymes of Streptococcus pyogenes that have the ability to cleave specific peptide bonds within the hinge region of the antibody and deglycosylate the molecule leading to loss of its effector functions, including activation of complement cascade by classical pathway and bridgement of cytotoxic cells. This forms the basis for development of enzyme-based interventions for antibody-mediated clinical conditions including various autoimmune disorders, organ rejection during transplantations, and therapeutic viral vector destruction. The specificity of these enzymes is exploited in efficient proteolytic processing of anti-cancer monoclonal antibodies for their characterization and production of clinically-important fragments. Use of antibody-degrading enzymes in clinical settings comes with some unmet challenges in terms of safe application, economical production, efficient immobilization, patient-friendly delivery, and limited scope.