A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

Donald M. O’Rourke,1 MacLean P. Nasrallah,2 Arati Desai,3 Jan J. Melenhorst,4 Keith Mansfield,5 Jennifer J. D. Morrissette,6 Maria Martinez-Lage,2 Steven Brem,1 Eileen Maloney,1 Angela Shen,7 Randi Isaacs,5 Suyash Mohan,8 Gabriela Plesa,4 Simon F. Lacey,4 Jean-Marc Navenot,4 Zhaohui Zheng,4 Bruce L. Levine,4 Hideho Okada,9 Carl H. June,4 Jennifer L. Brogdon,5 Marcela V. Maus10 1Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 2Division of Neuropathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 3Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 4Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA. 5Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. 6Division of Precision and Computational Diagnostics, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 7Novartis Oncology, East Hanover, NJ 07936, USA. 8Division of Neuroradiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. 9Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA. 10Cellular Immunotherapy Program, Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA.