Monoclonal Antibody-Based Therapies for Bacterial Infections
Purpose of review
This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials.
Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. While other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states.
Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.
Keywords: Monoclonal Antibody Therapy, Antibiotic Alternatives, Infections
From their initial development by murine hybridoma technology, to advancements in screening and modern engineering of humanized antibodies, monoclonal antibodies (mAbs) have grown rapidly in their therapeutic potential (1). Over 70 mAbs have been approved for human use, and eight times that many are in clinical development (2). Furthermore, with traditional antibiotics becoming increasingly obsolete due to antimicrobial resistance (AMR), mAbs are making a comeback in the field of anti-infective drugs alongside phage therapy and other historic strategies (1, 3). After being overshadowed for years by successes in anti-cancer and anti-immune antibody therapies, efforts to engineer mAbs against pathogens have finally yielded fruit, with four FDA certifications and a growing number of promising clinical trials (3, 4). However many hurdles remain in the field of anti-infective mAbs: finding optimal targets for a pathogen, understanding how the Fc receptor (FcR), isotype, and other structural regions mediate protection, and developing better pre-clinical and clinical trials to investigate the therapeutic potential of these antibodies. This review examines recent efforts pertaining to these pursuits.
Antibodies against Bacterial Toxins
Antibody therapies against infections have targeted numerous bacterial epitopes and virulence factors (), the first efforts focusing primarily on toxin neutralization. Indeed, all three currently-licensed FDA therapies against bacteria target bacterial exotoxins (4). Anti-toxin mAb therapies are thought to inhibit the virulence of the organism to limit invasion or damage to the host, without creating selective pressures on the organism.