323.292.2002 connect@NCCPRE.org

Christine E. Brown, Ph.D., Darya Alizadeh, Ph.D., Renate Starr, M.S., Lihong Weng, M.D., Jamie R. Wagner, B.A., Araceli Naranjo, B.A., Julie R. Ostberg, Ph.D., M. Suzette Blanchard, Ph.D., Julie Kilpatrick, M.S.N., Jennifer Simpson, B.A., Anita Kurien, M.B.S., Saul J. Priceman, Ph.D., Xiuli Wang, M.D., Ph.D., Todd L. Harshbarger, M.D., Massimo D’Apuzzo, M.D., Julie A. Ressler, M.D., Michael C. Jensen, M.D., Michael E. Barish, Ph.D., Mike Chen, M.D., Ph.D., Jana Portnow, M.D., Stephen J. Forman, M.D., and Behnam Badie, M.D.
N Engl J Med 2016; 375:2561-2569December 29, 2016DOI: 10.1056/NEJMoa1610497

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes — infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362.)

Supported by grants from Gateway for Cancer Research (G-14-600), the Food and Drug Administration (R01FD005129), the California Institute for Regenerative Medicine (CIRM; TR3-05641), the CIRM Alpha Stem Cell Clinics Network (AC1-07659), and the National Cancer Institute (NCI) and National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH) (P30CA33572, R01CA155769, R21NS081594, and R21CA189223).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Forman and Badie contributed equally to this article.
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or of the California Institute for Regenerative Medicine or any other agency of the State of California.

We thank Wen-Chung Chang, Nima Jamjampour, Alina Oancea, Alexandra Pike, Lauren Quezada, Laurelin Wolfenden, Sarah Wright, and Jingying Xu for T-cell manufacturing and product release; Alfonso Brito, Vivian Chiu, Cindy (Xin) Yang, and the staff at the City of Hope Clinical Immunobiology Correlative Studies Laboratory, Pathology Core and Cytogenetics Core Laboratory for their technical assistance; and Sandra Thomas for her critical review and editing of an earlier version of the manuscript.

From the Department of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory (C.E.B., D.A., R.S., L.W., J.R.W., A.N., J.R.O., A.K., S.J.P., X.W., S.J.F.), and the Departments of Information Sciences (M.S.B.), Clinical Research (J.K., J.S.), Neurosurgery (T.L.H., M.C., B.B.), Pathology (M.D.), Diagnostic Radiology (J.A.R.), Developmental and Stem Cell Biology (M.E.B.), and Medical Oncology and Therapeutics Research (J.P.), City of Hope Beckman Research Institute and Medical Center, Duarte, CA; and the Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle (M.C.J.).
Address reprint requests to Dr. Badie at the City of Hope Beckman Research Institute and Medical Center, 1500 E. Duarte Rd., Medical Office Bldg., 2nd Fl., Rm. 2001, Duarte, CA 91010-3000, or at bbadie@coh.org.