The pharmacokinetic-pharmacodynamic relationship is extremely complex and tumour drug penetration is one key parameter influencing therapeutic efficacy. In the context of antibody-drug conjugates (ADCs), which has undergone many innovation cycles and witnessed many failures, this feature is being addressed by a number of alternative technologies. Immunoglobulin-based ADCs continue to dominate the industrial landscape, but smaller formats offer the promise of more-effective cytotoxic payload delivery to solid tumours, with a higher therapeutic window afforded by the more rapid clearance. To make these smaller formats viable as delivery vehicles, a number of strategies are being employed, which will be reviewed here. These include identifying the most-appropriate size to generate the larger therapeutic window, increasing the amount of functional, cytotoxic payload delivered through conjugation or half-life extending technologies or other ways of extending the dosing without inducing toxicity.
Keywords: antibody–drug conjugate; fragments; scaffolds; solid tumours.
Published by Oxford University Press on behalf of Antibody Therapeutics 2020.