A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types.

ABSTRACT: Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. Currently, the complexity of these effector-target interactions and the donor-to-donor variations in NK cell receptor (NKR) repertoire require functional assays to be performed experimentally for each manufactured CAR-NK cell product and target combination. Here, we developed a computational mechanistic multiscale model which considers heterogenous expression of CARs, NKRs, adhesion receptors and their cognate ligands, signal transduction, and NK cell-target cell population kinetics. The model trained with quantitative flow cytometry and in vitro cytotoxicity data accurately predicts the short- and long-term cytotoxicity of CD33CAR-NK cells against leukemia cell

SUBMITTER: Ahmad S 

PROVIDER: S-EPMC11722217 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature