Single-Cell Intravital Microscopy of Trastuzumab Quantifies Heterogeneous in vivo Kinetics.

ABSTRACT: Cell-to-cell heterogeneity can substantially impact drug response, especially for monoclonal antibody (mAb) therapies that may exhibit variability in both delivery (pharmacokinetics) and action (pharmacodynamics) within solid tumors. However, it has traditionally been difficult to examine the kinetics of mAb delivery at a single-cell level and in a manner that enables controlled dissection of target-dependent and -independent behaviors. To address this issue, here we developed an in vivo confocal (intravital) microscopy approach to study single-cell mAb pharmacology in a mosaic xenograft comprising a mixture of cancer cells with variable expression of the receptor HER2. As a proof-of-principle, we applied this model to trastuzumab therapy, a HER2-targeted mAb widely used for treating breas

SUBMITTER: Li R 

PROVIDER: S-EPMC7028488 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature