Nanobody-as versatile tool emerging in autoimmune diseases

Nanobody (Nb) is derived from the variable domain of heavy-chain antibody (HCAb), naturally displaying notable properties like nano-scale size, exceptional stability, high specificity, low immunogenicity, and cryptic epitope accessibility. These features contribute to its great therapeutic potential as a valuable research tool across diverse diseases, especially autoimmune diseases (AIDs). Caplacizumab (Cablivi®) is the first nanobody drug approved for treating acquired thrombotic thrombocytopenic purpura (aTTP). This review summarizes the biomolecular structure, usage of Nb as a foundation of recombinant constructs, and biochemical properties of nanobodies. As attractive therapeutic candidates, many clinical trials of Nbs have been conducted, elucidating potential therapeutic strategies for AIDs. Therefore, the preclinical development and application of Nbs in AIDs are emphasized throughout this review. This review provides a comprehensive overview of nanobodies, emphasizing their immense potential as attractive therapeutic candidates for the application in the clinical treatment of autoimmune diseases (AIDs). • Nanobodies are derived from variable domains of heavy-chain antibodies, and naturally display many extraordinary properties. • The biomolecular structure, the use of nanobodies as modular elements to produce highly standardized recombinant constructs, and biochemical properties of nanobodies are reviewed. • The development and application of nanobodies in the field of autoimmune diseases are exclusively emphasized in this review.