• Christine E Brown, Behnam Badie, Michael E Barish, Lihong Weng, Julie R Ostberg, Wen-Chung Chang, Araceli Naranjo, Renate Starr, Jamie Wagner, Christine Wright, Yubo Zhai, James R Bading, Julie A Ressler, Jana Portnow, Massimo D'Apuzzo, Stephen J Forman, and Michael C Jensen.
• Department of Cancer Immunotherapy and Tumor Immunology, City of Hope Beckman Research Institute and Medical Center, Duarte, California. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Beckman Research Institute and Medical Center, Duarte, California. cbrown@coh.org.
• Clin Cancer Res. 2015 Sep 15; 21 (18): 4062-72.

PurposeA first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)-engineered, autologous primary human CD8(+) cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM).Experimental DesignThree patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8(+) CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 10(8) CAR-engineered T cells via a catheter/reservoir system.ResultsWe demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine(+) CTL clones into the resection cavity of 3 patients with recurrent disease was well-tolerated, with manageable temporary brain inflammation. Following infusion of IL13-zetakine(+) CTLs, evidence for transient anti-glioma responses was observed in 2 of the patients. Analysis of tumor tissue from 1 patient before and after T-cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine(+) T-cell administration.ConclusionsThese findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T-cell therapies can be applied.©2015 American Association for Cancer Research.

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