Method Profile
Systemic pharmacokinetics, single-cell disposition and tumor distribution are combined to compare free-MMAE exposure and efficacy rankings for three ADCs.
Early research comparison of vc-MMAE ADC candidates using tumor payload exposure and in vitro cytotoxicity.
A multiscale QSP model evaluated for RC48, RC108 and RC118, which target different antigens.
Computational candidate comparison with xenograft exposure and efficacy data as the experimental reference.
Candidates
RC48, RC108 and RC118: three vc-MMAE ADCs.
Reference measurements
Xenograft-tumor unconjugated-MMAE exposure, observed efficacy rankings and in vitro cytotoxicity IC50.
Model scales
Systemic PK, single-cell disposition and spatial tumor distribution.
Combine simulated exposure and payload distribution with in vitro cytotoxicity, then assess agreement with the observed candidate ranking.
The model is evaluated against xenograft exposure data and used to reproduce the efficacy ranking of three ADCs.
Three ADCs: RC48, RC108 and RC118.
Predicted intratumoral free-MMAE exposure and ranking versus xenograft observations.
Exposure prediction errors ranged from −38.13% to 20.52%; integration with in vitro IC50 reproduced the observed three-ADC efficacy ranking.
The model links systemic pharmacokinetics, cellular disposition and tumor distribution. Combining predicted free-payload exposure with in vitro cytotoxicity reproduced the observed efficacy ranking of three ADCs in xenograft models.
