Diagnostic and therapeutic targeting of EGF-receptor positive cancer cells using single-domain antibodies

Single-domain antibodies (sdAbs) provide several advantages over classical antibodies and fragments thereof. Due to their small size and strict monomeric appearance combined with other important properties such as high solubility and stability as well as high specificity and affinity for the respective antigen, these proteins have been identified as attractive targeting moieties for molecular imaging and drug delivery. Furthermore, sdAbs are easily engineered into bivalent and bispecific constructs by genetic in-frame joining of two identical or two different sdAbs, respectively. This results in increased antigen binding through avidity effects and in enhanced construct specificity by simultaneous interaction with two different antigens, respectively.
In addition to intrinsic agonistic or antagonistic effects on their target, sdAbs appear to be ideally suited to create novel tailored derivatives equipped with innovative effector functions. The chemical or genetic linkage of sdAbs to accessory effector moieties such as toxins and enzymes results in a new class of target-specific anticancer therapeutics. Thereby, the sdAb guides the effector moiety to the diseased tissue, where it carries out its particular function.
Herein the application of radiolabelled epidermal growth factor receptor (EGFR) specific sdAbs as in vivo molecular imaging tracers as well as their intrinsic antagonistic effects on tumor cells will be described. Furthermore, the construction and characterisation of sdAb-based therapeutics will be exemplified. Thus, this contribution sheds light on the future application of sdAb derivatives in the field of cancer diagnosis and therapy.