Nanobodies as novel agents for cancer therapy

Abstract

Nanobodies are the smallest fragments of naturally occurring heavy-chain antibodies that have evolved to be fully functional in the absence of a light chain. As such, the cloning and selection of antigen-specific nanobodies obviate the need for construction and screening of large libraries, and for lengthy and unpredictable in vitro affinity maturation steps. The unique and well-characterised properties enable nanobodies to excel conventional therapeutic antibodies in terms of recognising uncommon or hidden epitopes, binding into cavities or active sites of protein targets, tailoring of half-life, drug format flexibility, low immunogenic potential and ease of manufacture. Moreover, the favourable biophysical and pharmacological properties of nanobodies, together with the ease of formatting them into multifunctional protein therapeutics, leaves them ideally placed as a new generation of antibody-based therapeutics. This review describes the state of the art on nanobodies and illustrates their potential as cancer therapeutic agents.