Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections

Abstract

Introduction: Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely.

Aim: This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics.

Material and methods: A literature review was conducted addressing the following topics about antibody-antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages.

Result: Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells.

Conclusion: A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

Keywords: antibodies; antibody‐based therapy; immune system; pharmacokinetic.

FIGURE 1

Mechanism of killing bacteria by antibody–antibiotic conjugates (AAC). AAC binds bacteria and the host cells internalize AAC‐bound bacteria. In the next Step, fusion occurs with the phagolysosome where lysosomal cathepsins cleave the VC linker, releasing AAC. Then unconjugated AAC kills the intracellular bacteria.

FIGURE 2

Antibody–antibiotic conjugates (AAC) mechanism for killing Staphylococcus aureus. DSTA4637S mechanism for killing intracellular S. aureus. Step 1, DSTA4637S binds S. aureus. Step 2, host cells internalize DSTA4637S‐bound S. aureus. Step 3, fusion occurs with the phagolysosome where lysosomal cathepsins cleave the VC linker, releasing dmDNA31. Step 4, unconjugated dmDNA31 kills the intracellular bacteria.

FIGURE 3

Antibody–antibiotic conjugates (AAC) structure.

FIGURE 4

Advantages and overall structure of antibody–antibiotic conjugates (AAC). (A) Antibiotic delivery and opsonization: AACs enable precise delivery of antibiotics to target bacteria, ensuring efficient opsonization for enhanced phagocytosis. (B) Specificity: AACs exhibit high specificity by targeting surface antigens on bacteria, minimizing off‐target effects on host cells. (C) Fc‐mediated uptake: AACs utilize Fc receptors (FcR) to facilitate uptake by immune cells, enhancing the clearance of intracellular bacteria. (D) Release and active antibiotic in specific conditions: Within intracellular environments like phagolysosomes, AACs release active antibiotics, ensuring effective bacterial eradication. (E) Effective in antibiotic‐resistant bacteria: AACs demonstrate efficacy even against antibiotic‐resistant bacterial strains, addressing the challenge of antibiotic resistance.