CISH locus-targeted FAPα CAR-T cells

CISH locus-targeted FAPα CAR-T cells represent a novel, non-viral Chimeric Antigen Receptor (CAR-T) cell therapy developed to address the challenges of treating Glioblastoma (GBM), including antigenic heterogeneity and immunosuppression. This therapy involves engineering T cells to express a CAR that specifically targets Fibroblast Activation Protein α (FAPα), an antigen commonly found on both GBM cells and their associated stromal cells. Simultaneously, the intracellular immune checkpoint CISH is knocked out (KO) at its genomic locus using cssDNA-based CRISPR-Cas9-mediated site-specific integration technology. This dual strategy aims to enhance the proliferative capacity and cytotoxic activity of the CAR-T cells against FAPα-positive targets, thereby improving anti-GBM efficacy.