Talk by Prof. Franklin at Dies Academicus

Bad Memories - targeting inflammation with alpaca-derived nanobodies

The talk will be about how inflammation protects us against infection and injury. In chronic inflammatory diseases, however, it fails to subside and slowly damages tissues over years. One reason is that inflammation leaves behind clumps of protein that persist in tissues and keep the immune system on alert. Current treatments block the chemical messengers that drive inflammation. They ease symptoms, but they leave these clumps in place, often weaken the body’s defenses against infection, and must be taken for life. We discovered that some of these clumps come from the immune system’s own alarm machinery, the inflammasome. When immune cells sense danger, a protein called ASC assembles into large aggregates, known as “specks”. Cells can release these specks, which then accumulate in tissues, prolong inflammation, and promote the formation of amyloid, fibrous protein deposits found in many chronic inflammatory diseases. To remove the specks, we turned to alpacas. Like camels and llamas, alpacas make unusually small antibodies. From these, we developed nanobodies that recognize ASC specks and break them apart. In mice, the nanobodies reduced inflammation in models of gout, rheumatoid arthritis, and pancreatic cancer. Because they act only on specks that cells have already released, they spare the early immune response that protects us from infection. Instead of suppressing the immune system indefinitely, this approach removes a persistent driver of inflammation and could lead to safer, more effective treatments for chronic inflammatory diseases.