Nanobodies as therapeutics: big opportunities for small antibodies

• Nanobodies (Nbs) are camelid-derived single-domain antibodies.
• Nbs have powerful binding and inhibitory capacity with great therapeutic potential.
• Nbs are used in cancer, infections, inflammation and neurodegeneration.
• Several clinical trials with Nbs are on-going.

Members of the Camelidae (including camels and llamas) produce, in addition to conventional antibodies (Ab), a unique type of Ab that lacks light chains. The variable antigen-binding domains derived from these Ab are named ‘nanobodies’ (Nbs). Nbs exert high specificity and affinity and, when properly selected, are more stable than conventional Ab. Furthermore, their toxicity and immunogenicity are both low. They are easy to produce and their modularity makes them amenable for the generation of multivalent complexes. In this review, we discuss how Nbs are being explored as therapeutics in many fields of medicine, including oncology, inflammatory, infectious and neurological diseases, and imaging. In addition, we highlight their potential for use in the diagnosis and monitoring of diseases. Finally, we provide an extended overview of Nbs that are, or have been, involved in clinical trials.