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. 2020 Nov 25;3(4):237–245. doi: 10.1093/abt/tbaa024

Figure 1.

Figure 1

Drug conjugate delivery via the tumour vasculature and penetration can be illustrated with broadly three PK profiles. (A) Conventional ADCs with MWs of > 150 kDa accumulate and penetrate into tumours over days and eliminate from the body over weeks requiring less frequent dosing, but a higher risk of off-target/cumulative toxicity. (B) A wide range of smaller (5–100 kDa), protein-based binding scaffolds such as scFv and DARPins, which have uptake and penetration kinetics lasting hours, but are eliminated more rapidly (days), reducing non-specific exposure time, but may require strategies for higher drug delivery (e.g. higher DAR, HLE, more frequent or higher dosing). (C) Very small peptidic conjugates (<5 ka) that have very rapid and more complete uptake and penetration kinetics, but are eliminated in a matter of hours also requiring strategies to improve temporal exposure.