Computational analysis of 4-1BB-induced NFκB signaling suggests improvements to CAR cell design.

ABSTRACT:

Background

Chimeric antigen receptor (CAR)-expressing cells are a powerful modality of adoptive cell therapy against cancer. The potency of signaling events initiated upon antigen binding depends on the costimulatory domain within the structure of the CAR. One such costimulatory domain is 4-1BB, which affects cellular response via the NFκB pathway. However, the quantitative aspects of 4-1BB-induced NFκB signaling are not fully understood.

Methods

We developed an ordinary differential equation-based mathematical model representing canonical NFκB signaling activated by CD19scFv-4-1BB. After a global sensitivity analysis on model parameters, we ran Monte Carlo simulations of cell population-wide variability in NFκB signaling and quantified the mutual information between the ext

SUBMITTER: Tserunyan V 

PROVIDER: S-EPMC9413922 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature