The overuse of antibiotics is increasingly leading to the emergence of infectious superbugs—dangerous bacteria that have developed antimicrobial resistance (AMR) and are therefore much harder, if not impossible, to eliminate from the body. In a review publishing in the Cell Press journal Trends in Immunology on May 27, researchers highlight the promise of using human monoclonal antibodies (mAbs) to treat patients more effectively and tackle AMR.
"The strategy of solving AMR using only new antibiotics has failed completely and is generating monster bacteria that are resistant to all of them," says the paper's corresponding author, Rino Rappuoli of Fondazione Biotecnopolo di Siena in Italy. "AMR needs to be addressed with multiple and differentiated strategies, and vaccines and mAbs are the most promising tools."
mAbs are lab-made immune proteins that can target proteins present on human or harmful bacterial cells very precisely. Over the past several decades, mAbs have become important in medicine, with more than 150 approved for the treatment of cancer, autoimmune and inflammatory disorders, and other conditions. The authors say now is the time to focus on developing mAbs to target bacteria and treat infections.
"There is strong preclinical evidence that mAbs can be a solution when antibiotics fail," Rappuoli says.
One benefit is that unlike broad-spectrum antibiotics, which often kill helpful bacteria in the body in addition to the harmful ones, mAbs can be designed to target only the disease-causing bacteria, thereby protecting the microbiome.
Antimicrobial mAbs can also combat drug-resistant infections in ways antibiotics cannot, enabling them to work against strains that have evolved resistance to traditional antibiotics. For example, they may block bacteria from releasing toxins, preventing the damage that these toxins cause. They can also "tag" bacteria to make them more recognizable to the immune system and stop bacteria from attaching to or invading human cells, preventing them from forming protective biofilms, which make bacteria harder to penetrate with traditional antibiotics.
Scientists are improving mAbs using new technologies like antibody engineering, mRNA delivery, and artificial intelligence. Some researchers are even combining antibodies with other drugs to create targeted treatments.
The authors hope this paper will help spread the word among students, scientists, investors, clinicians, and policymakers about the potential of using mAbs to combat AMR. They also acknowledge challenges in developing mAbs into effective drugs for AMR. Better tools, including human serum containing the appropriate immune cells, as well as appropriate in vivo and in vitro models, are needed.
"But the most important obstacle to transforming mAbs into effective drugs for AMR is the absence of an attractive market for antimicrobial drugs more broadly. The other is the high price of developing mAbs," Rappuoli says.
"We are working on alternative ways of manufacturing antibodies, which should reduce the time of development and the cost. This would help to make them more accessible to people all over the world, not only in wealthy countries."
