Camelid Single-Domain Antibodies for Targeting Cancer Nanotheranostics

Single-domain antibodies (VHHs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies, are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs or targeting agents. The high stability of VHHs against high concentrations of organic solvents and extreme pHs and temperatures opens a wide range of applications for the detection of small molecules such as the development of more efficient methods of immobilization for biosensing purposes in addition to attachment sites in several immunotherapeutic constructs such as chimeric T cell therapy. VHHs, due to their unique 3D structure, have versatile abilities to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This chapter summarizes the applications and great potentials of VHHs as therapeutic tools or noninvasive in vivo molecular imaging agents. Moreover, the unique properties of VHHs are outlined like internalization, size, thermal and chemical stability, affinity, blood clearance, and labeling procedures. We highlight some already-reported therapeutic examples about VHHs being used for the treatment of several diseases such as cancer and several nanostructures which are used as molecular imaging or delivering tools.