Introduction to Nanobodies

A naturally occurring antibody devoid of light chains present in the peripheral blood of camel species such as alpaca is the natural dimer composed of two heavy chains, also called the heavy-chain antibody. The variable region of this heavy-chain antibody, called VHH, is capable of binding antigen as a single molecule and has high affinity and specificity. With a size of below 15 kDa and dimensions in the nanometer range (~2.5 nm in diameter and ~4 nm in height), the VHH molecule was also named nanobody. Not as easy to adhere and aggregate to each other as artificially modified single-chain fragment variable (scFV), VHH is more stable and can even be stored at room temperature, and can be used to construct bifunctional domain or trifunctional domain antibodies that recognize HSA or construct the form of Fc fusion protein to prolong the half-life of nanobodies, so as to manufacture desired antibody drugs. In recent years, nanobodies have shown unique value in the development of applications as extracellular antigen recognition domain of CAR-T cell agents, and marketed CAR-T drugs and many CAR-T cell agents under development have verified the druggability of nanobodies in CAR-T drug development.