Exploring alternative antibody scaffolds: Antibody fragments and antibody mimics for targeted drug delivery

The field of targeted therapeutics has benefitted immeasurably from the development of high-affinity antibodies. These important ligands have facilitated the development of effective therapies, particularly when conjugated to potent cytotoxic payloads i.e. in antibody–drug conjugates (ADCs). The success of ADCs is evidenced by rapid adoption within the pharmaceuticals community; many major companies have dedicated ADC research programmes. However, despite the advantages, the field of ADCs has failed to live up to its full potential. Studies have emerged suggesting that traditional IgG scaffolds may not be the optimal format for targeted payload delivery. In response, the protein engineering community has begun to explore alternative high-binding protein scaffolds as antibody mimics. In this short review I will summarise the generation, modification, and application of emerging antibody fragments and synthetic antibody mimics, with a focus on their use as drug carriers. The review aims to highlight the advantages of antibody mimics, and how they could be employed to overcome the issues and limitations of traditional ADCs.