Phase 1 EGFR/IL13Rα2 pool-CAR T cells target EGFR + IL13Rα2 in HGG

City of Hope Medical Center is running a Phase 1, first-in-human, open-label, dose-finding study of autologous “pool-CAR” T cells engineered to recognize EGFR and IL13Rα2 on tumor cells (dual-antigen CAR T targeting), delivered locoregionally into the CNS via an intracranial/intraventricular catheter. The goal is to define safety, feasibility, and a recommended dose while looking for early anti-tumor signals in recurrent or progressive high-grade glioma, including progressive glioblastoma and grade 3–4 IDH-mutant astrocytoma with IL13Rα2 expression and an EGFR alteration (a molecularly selected subset rather than all comers). Patients undergo leukapheresis, then neurosurgical resection/biopsy and catheter placement, followed by weekly CAR T infusions for up to 4 cycles (with the option for additional cycles), alongside intensive MRI/PET and CSF sampling. The scientific angle is the intracranial delivery strategy (to bypass blood–brain barrier limitations) paired with antigen pooling to reduce antigen-escape, building on City of Hope’s prior IL13Rα2 CAR T experience in glioma. Today’s care for recurrent/progressive HGG is repeat surgery when feasible, focal re-irradiation in select patients, temozolomide or nitrosoureas (e.g., lomustine), bevacizumab for symptom control, and clinical trials—none of which are reliably durable for most patients.