Camels for Health: Development of Nanobody Research

Scientific discoveries and advancements have historically come from improving our understanding of the natural world and its biological processes. The most notable example in the biological sciences is the discovery of penicillin by Sir Alexander Fleming in 1928 and his famous remark, “Nature makes penicillin; I just found it.” Penicillin, which is produced by the mould Penicillium notatum and inhibits the growth of Staphylococcus bacteria, was the first effective antibiotic against bacterial infections. This discovery not only transformed medical practice but also created the field of targeted bacterial inhibition and set the cornerstone of modern antimicrobial therapy. The discovery of unique antibodies in dromedaries (Camelus dromedarius) by Professor Raymond Hamers and his research team at Vrije Universiteit Brussel, Belgium, in the late 1980s followed a similar path. Conventional immunoglobulins or antibodies are composed of two heavy and two homodimeric light chains. They are produced by almost all mammals, including South American camelids and camels as well as humans, as a second line of defence mechanism against invading pathogens and have a central role in the health and well-being of living organisms. However, the Camelidae family has been shown to possess a unique, smaller immunoglobulin subclass that contains the heavy chain, but lacks the light chain (referred to as heavy chain only antibodies or HCAbs). These are naturally occurring, distinct from other genetically engineered antibody fragments. In recent years, HCAbs and specifically nanobodies have gained particular attention in human health research. Nanobodies have unique biophysico-chemical characteristics which can serve as building blocks for the development of therapeutics against cancer, inflammation, neurodegenerative diseases, and infectious diseases. The first nanobody-based therapeutic, caplacizumab, was approved by the FDA in 2019 as a drug for human application to treat acquired thrombotic thrombocytopenic purpura disorder. In this chapter, we provide a historical perspective on the discovery of camelid antibodies and their applications in human health and well-being.