Open AccessTackling solid tumour therapy with small-format drug conjugates
Author(s) -
Mahendra P. Deonarain,
Quinn Xue
Publication year - 2020
Publication title -
antibody therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.579
H-Index - 5
ISSN - 2516-4236
DOI - 10.1093/abt/tbaa024
Subject(s) - payload (computing) , therapeutic window , pharmacodynamics , context (archaeology) , dosing , drug , drug delivery , therapeutic index , computer science , pharmacokinetics , conjugate , medicine , pharmacology , nanotechnology , biology , mathematics , materials science , computer network , paleontology , network packet , mathematical analysis
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.