ATIM-13. PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTOR-ENGINEERED T CELLS TARGETING IL13Rα2 FOR THE TREATMENT OF GLIOBLASTOMA

Abstract

T cell immunotherapy is emerging as a powerful strategy to treat cancer, and may offer opportunities to improve outcomes for patients with glioblastoma (GBM). We have optimized a chimeric antigen receptor (CAR) T cell therapy targeting the GBM-associated antigen IL13Rα2 that utilizes CD62L-enriched central memory T cells (Tcm) engineered by lentiviral transduction to express a second-generation 4-1BB-containing CAR (IL13BBζ). We report here initial findings from our first-in-human clinical trial [NCT02208362]. The aims of this trial include, (1) evaluation of the safety and feasibility of targeting IL13Rα2; and (2) comparison of intracranial delivery through intratumoral (with and without tumor resection) and intraventricular routes. To date, we have treated 10 patients and completed the first low-dose cohort of three resection patients. Local intracranial delivery of weekly IL13BBζ Tcm infusions has been safe and well-tolerated. Persisting CAR T cells were detected in the tumor cyst fluid or cerebral spinal fluid for a minimum of 7 days for patients with samples available. Evidence for CAR T cell bioactivity has been observed in a subset of patients, including decreased IL13Rα2 tumor antigen expression post-treatment. One patient of particular interest with recurrent multifocal GBM that included metastatic sites in the spine, was first treated with six weekly infusions of IL13BBζ Tcm into the resection cavity of the largest tumor, followed by ten weekly intraventricular infusions. In the absence of any other therapeutic interventions, this patient experienced a dramatic antitumor response with all intracranial and spinal tumors regressing 79%-97% by maximum area. This response was sustained for more than 7-months post-initiation of CAR T cell treatment. These early clinical findings suggest that intracranial delivery of second-generation IL13Rα2-targeted CAR T cells is safe and well-tolerated, and that CAR T cells are capable of eliciting potent antitumor responses against recurrent glioblastoma.