Efficacy of mRNA multi-targeting CAR T for glioblastoma
Dagher OK, Pedard M, Bedoya DM, et al. Preclinical Efficacy of Multi-Targeting mRNA-Based CAR T Cell Therapy in Resection Models of Glioblastoma. Molecular Therapy. 2025; (doi: 10.1016/j.omtn.2025.102676).
Scientists have developed a model to assess the efficacy of mRNA-based chimeric antigen receptor (CAR) T cells, which are understudied despite their potential in treating glioblastoma (GBM) and other resectable solid tumors. While mRNA designs could possibly overcome issues with persistence, tumor heterogeneity, and additional challenges seen when deploying traditional viral-transduced CAR T cells to solid tumors, existing preclinical platforms for CAR T observation and assessment may not be optimal for mRNA constructs. To address this shortcoming, the proposed strategy uses mRNA-based CAR T cells in conjunction with multi-targeting of GBM-associated receptors and near-total resection surgery to deliver a simple model for assessing mRNA CAR T-cell performance in solid tumors. Based on in vitro and in vivo analyses of mRNA-based CAR T cells under various conditions and using different delivery methods, researchers documented a therapeutic window of anti-tumor efficacy and robust and durable complete remissions in xenograft mouse models of GBM with maximal surgical resection and locoregional delivery of multivalent CAR T cells.