Miniaturised ‘antibody’-drug conjugates for solid tumours?

With Antibody-Drug Conjugate strategies firmly focussed on the precise conjugation to the large protein Immunoglobulin-G format, it is easy to miss the more recent technological innovations in small-format drug conjugates. Here, the targeting ligand can be at 50–95% reduced in size, or even smaller if peptidic in nature. Antibody domains or alternative binding scaffolds, chemically-modified with ultra-potent cytotoxic payloads offer an alternative approach for oncology therapeutics, promising a wider therapeutic window by virtue of superior solid tumour penetration properties and more rapid system clearance. Many of the traditional ADC concepts still apply, but as these miniaturised ADCs enter the clinic over the next 2–3 years, we will learn whether these new features translate to patient benefits.