Mechanistically modeling peripheral cytokine dynamics following bispecific dosing in solid tumors.

ABSTRACT: Bispecific antibodies exhibit proven clinical benefit, and many bispecifics are currently in clinical development for oncology. Cytokine release syndrome (CRS) is a common clinical adverse effect observed following CD3-based bispecific dosing. However, the pathophysiology of CRS is not fully understood, and no computational model mechanistically describing clinical cytokine dynamics following bispecific dosing in solid tumors exists. Here, a quantitative systems pharmacology (QSP) model describing peripheral clinical cytokine dynamics following bispecific dosing in solid tumors is presented. Using tebentafusp as a case study, a CD3-bispecific approved for uveal melanoma, the model successfully captures the dynamics of five cytokines. The QSP model was shown to predict observed phenomena, s

SUBMITTER: Weddell J 

PROVIDER: S-EPMC10681545 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature