![]() For biological therapies in particular, the relationship between drug dosing and tumour uptake is highly complex and very often, the micro-distribution across a whole tumour does not correlate with drug dose or plasma concentration and this underappreciated variability could explain poor responses due to suboptimal concentrations of therapeutic agents in the tumour micro-environment (TME). 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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