CAR T therapy is a new approach to improving the treatment of recurrent high-grade glioma, a type of brain cancer that is hard to treat with existing methods. This summary describes a completed early-stage (phase I) clinical trial that tested CAR T cells designed to target a protein called IL-13Rα2 in 65 patients with recurrent high-grade glioma, most of whom had recurrent glioblastoma (rGBM). The main goals were to check the safety and practicality of the treatment, find the best dose for future trials. Secondary goals included looking at patient survival, how the disease responded to the treatment, and changes in patients’ immune system tumor environment. The trial tested three ways of delivering the CAR T cells directly to the brain: into the tumor (ICT), into the brain’s fluid-filled spaces (ICV), and a combination of both. It also tested two different ways of making the CAR T cells. The direct brain delivery methods were practical and generally safe, with no severe side effects limiting the dose. The most serious treatment-related side effects were one case of brain dysfunction (grade 3 encephalopathy) and one case of poor muscle coordination (grade 3 ataxia). Half of the patients (29 out of 58) experienced stable disease or better, with two showing partial tumor shrinkage, one showing complete tumor disappearance, and another showing complete disappearance after additional CAR T treatment outside the trial. For rGBM patients, the average survival time was 7.7 months, with those in the final part of the trial living an average of 10.2 months. The treatment was linked to increases immune activity, and higher levels of certain immune cells in the tumor before treatment were linked to better survival. These results suggest that this IL-13Rα2 CAR T therapy is safe and shows potential for helping some patients with this challenging type of brain cancer.