Biofilms are complex microbial communities, surface attached and held together by self-produced polymer matrices. These matrices are mainly composed of polysaccharides, secreted proteins and nucleic acids. Poly-N-acetyl glucosamine (PNAG) is a highly conserved surface polysaccharide expressed by a range of bacterial, fungal and protozoan microorganisms. It is associated with microbial biofilm formation. Partial deacetylation of PNAG (dPNAG) is critical for the function of PNAG in biofilm formation and required for the structural development and integrity of biofilm. Antibodies to PNAG and/or dPNAG have significant potential as broad-spectrum therapeutics for a range of bacterial and fungal infections. Research suggests that dPNAG is a better target than PNAG for antibody-based therapeutics; however, identification of dPNAG antibodies has been challenging.
Researchers at the National Cancer Institute (NCI) identified a human antibody, denoted TG10, that selectively binds to dPNAG with potential as a novel antimicrobial agent. F598, a human IgG1 monoclonal antibody (mAb) which binds to both PNAG and dPNAG, is in active development as a potential antimicrobial agent in clinical trials. The novel antibody TG10 binds to a different location on the biofilm and shows synergistic effects when administered in combination with F598. The TG10 antibody has been tested both in vitro and in vivo and shows good efficacy both alone and in combination with F598.
Possible combinatorial or synergistic effect on existing dPNAG or PNAG antibodies.
Binds to a different location on dPNAG than the known dPNAG antibody F598
Suggestion that combination therapy with TG10 and F598 is superior to either as mono-therapy
F598 already used in human clinical trials; existing safety data could facilitate regulatory process of a combination therapy
- Therapeutic use against multiple microbial pathogens, either alone or in combination with other anti-PNAG/dPNAG agents
- Prophylactic use to prevent high-risk infections
- Diagnostic imaging (using labeled form of TG10)