The physiological limits of bispecific monoclonal antibody tissue targeting specificity.

ABSTRACT: Bispecific monoclonal antibodies (bsmAbs) are expected to provide targeted drug delivery that overcomes the dose-limiting toxicities often accompanying antibody-drug conjugates (ADC) in clinical practice. Much attention has been paid in the past to target selection, mAb affinities and the payload linker design, but challenges remain. Here, we demonstrate, by physiologically based pharmacokinetic (PBPK) in silico modeling and simulation, that the tissue-targeting accuracy of mono- and bispecific antibody therapeutics is substantially limited by normal physiological characteristics like organ volumes, blood flow rates, lymphatic circulation, and rates of extravasation. Only a small fraction of blood flows through solid tumor, where the diffusion-driven extravasation is relatively slow

SUBMITTER: Sepp A 

PROVIDER: S-EPMC12005452 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature