The efficacy of chimeric antigen receptor (CAR) T cell therapy for solid tumours has been disappointing to date. However, new data from a phase I trial in patients with recurrent high-grade gliomas (rHGGs) demonstrate the therapeutic potential of post-surgical intracranial delivery of CAR T cells targeting IL-13 receptor α2 (IL-13Rα2), a cancer-testis antigen that is often ectopically expressed in these hard-to-treat cancers.

The CAR T cells evaluated in this trial were designed to selectively target IL-13Rα2 over IL-13Rα1, a low-affinity isoform more ubiquitously expressed in non-malignant tissues, by using E12Y-mutated IL-13 ligand as the targeting moiety. CAR T cell manufacturing was successful for 89 of 92 patients with IL-13Rα2-expressing rHGGs who underwent apheresis, although rapid disease progression precluded surgery and/or CAR T cell infusion in 24. The remaining 65 patients were allocated to five treatment arms testing intratumoural CAR T cell delivery following either biopsy (arm 1; n = 2) or surgery (arm 2; n = 18), intraventricular delivery following surgery (arm 3; n = 11), or both routes (arms 4 and 5; n = 12 and 22, respectively); arm 5 also involved an optimized manufacturing process that enriches for naive, stem-cell memory and central memory T cells, as opposed to only the latter subset in arms 1–4.