BETting on BRD4 inhibition to combat adaptive resistance to CAR T cell therapy in glioblastoma

Abstract

In this issue of Molecular Therapy, Xia et al.1 demonstrate that chimeric antigen receptor (CAR) T cells engineered to recognize the epidermal growth factor receptor (EGFR) control glioblastoma multiforme (GBM) for a short time but then paradoxically potentiate adaptive resistance in tumors, whereby a battery of genes encoding various immunosuppressive molecules (i.e., programmed death-ligand 1 [PD-L1], programmed death ligand 2 [PD-L2], herpes virus entry mediator [HVEM], galectin-9 [Gal-9], indoleamine 2,3-dioxygenase 1 [IDO1], etc.) are upregulated during long-term therapy.