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.ĭrug penetration into solid tumours as a factor influencing efficacy has been discussed at length over the years, but is it only now being actively addressed. To make these smaller formats viable as delivery vehicles, a number of strategies are being employed, which will be reviewed here. 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. 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. The pharmacokinetic–pharmacodynamic relationship is extremely complex and tumour drug penetration is one key parameter influencing therapeutic efficacy.
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