Translational PK-PD model for in vivo CAR-T-cell therapy delivered using CAR mRNA-loaded polymeric nanoparticle vector.

ABSTRACT: Autologous chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable response rates, yet its widespread implementation is hindered by logistical, financial, and physical constraints. Additionally, challenges such as poor persistence and allorejection are associated with allogeneic cell therapies. An innovative approach involves in vivo transduction of endogenous T-cells through the administration of CAR mRNA encapsulated in polymeric nanoparticles (NPs), resulting in transient CAR surface expression on circulating T-cells. This method presents a promising alternative, although the dose-exposure-response relationship of in vivo CAR-Ts remains poorly elucidated. The transient nature of CAR expression may necessitate repeated dosing, potentially introducing additional hurdles

SUBMITTER: Kim SJ 

PROVIDER: S-EPMC11655386 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature