Predicting the Pharmacokinetics of T-Cell Engagers as a Function of Target-Mediated Drug Disposition.

ABSTRACT: T-Cell Engagers (TCEs) are biological multi-specific molecules designed to co-engage targets on T cells and on a target cell for destruction. Molecular formats are typically derived from IgG monoclonal antibodies or similar fusion proteins with FcRn-mediated recycling, such as albumin binders. Despite this similarity, TCEs are often observed to have much attenuated half-lives of a few days, compared to the weeks expected of IgG monoclonal antibodies; furthermore, the usual ranking of half-lives in humans being greater than those in the non-human primate (NHP) is not preserved and we demonstrate that the usual methods of PK scaling by allometry are poor predictors of human PK. The half-life of biological molecules may be reduced due to clearance from target-mediated drug disposition (TMDD).

SUBMITTER: Penney M 

PROVIDER: S-EPMC12597969 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature