Transient mRNA CAR T cells targeting GD2 provide dose-adjusted efficacy against diffuse midline glioma and high-grade glioma models.

ABSTRACT:

Background

Diffuse midline glioma (DMG) and high-grade glioma are devastating pediatric central nervous system tumors that remain incurable. Recent chimeric antigen receptor (CAR) T cell studies have shown proof of concept and early signs of efficacy against DMG targeting GD2. Prior work and ongoing clinical trials have focused on using viral vectors to create permanent CAR T cells. However, virally transduced GD2-directed CAR T cells have shown significant neurotoxicity in both preclinical models and human trials.

Methods

We evaluated transient CAR T cells targeting GD2 created with mRNA, assessing for efficacy and safety in cell line, organoid, and in vivo xenograft models with repetitive intratumoral dosing.

Results

We show that mRNA GD2-directed CAR T cells are ac

SUBMITTER: Foster JB 

PROVIDER: S-EPMC12833531 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature