In 1993, naturally occurring heavy-chain-only antibodies (HCAbs) were discovered. Compared to the heavy chain variable regions of traditional antibodies, the variable domain of heavy chain of HCAbs (VHH) from camelids (also known as nanobodies) have four aliphatic amino acid residues in the FR2 region replaced by hydrophilic amino acids. This substitution confers greater stability in the absence of a light chain.
Nanobodies are the smallest antigen-binding fragments found in nature. With a molecular weight of only 15 kDa, nanobodies offer great flexibility and are easy to use as components for constructing therapeutic molecules in innovative format such as multivalent and multispecific antibody molecular structures. Over the past 20 years, extensive research and development achievements have demonstrated the significant value of nanobodies in clinical therapeutic use.
Brand Disease Target Antigen Company Approval Status Cablivi® (caplacizumab- yhdp) Acquired thrombotic thrombocytopenicpurpura Von Willebrand factor Ablynx NV Approved (USA, EU) Carvykti® (Ciltacabtagene autoleucel) Refractory/relapsed multiple myeloma B-cell maturation antigen Legend Biotech/ Janssen Biotech, Inc Approved (USA, EU) Nanozora® (Ozoralizumab) Rheumatoid arthritis Tumor necrosis factor-alpha Ablynx NV/ Taisho Pharmaceuticals Holdings/ EddingPharm Approved (Japan) Enweida® (Envonolimab) MSI-H or dMMR adult advanced solid tumors Programmed death-ligand 1 Alphamab Oncology/ 3D Medicines, Inc./ Sim.
