Quantitative pharmacology of dual-targeted bicistronic CAR-T-cell therapy using multiscale mechanistic modeling.

ABSTRACT: Despite the initial success of single-targeted chimeric-antigen receptor (CAR) T-cell therapy in hematological malignancies, its long-term effectiveness is often hindered by antigen heterogeneity and escape. As a result, there is a growing interest in cell therapies targeting multiple antigens (≥2). However, the dose-exposure-response relationship and specific factors influencing the pharmacology of dual-targeted CAR-T-cell therapy remain unclear. In this study, we have developed a multiscale cellular kinetic-pharmacodynamic (CK-PD) model using case studies from CD19/CD22 and GPRC5D/BCMA autologous CAR-Ts. Initially, an in vitro tumor-killing model characterized the impact of individual binder affinities and their contribution to overall potency across varying (1) effector: target (ET) rat

SUBMITTER: Su MC 

PROVIDER: S-EPMC11812944 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature