Frontiers in Oncology (May 2021)
Case Report: Prolonged Survival Following EGFRvIII CAR T Cell Treatment for Recurrent Glioblastoma
- Joseph S. Durgin,
- Joseph S. Durgin,
- Joseph S. Durgin,
- Fraser Henderson,
- MacLean P. Nasrallah,
- MacLean P. Nasrallah,
- Suyash Mohan,
- Sumei Wang,
- Simon F. Lacey,
- Jan Joseph Melenhorst,
- Jan Joseph Melenhorst,
- Jan Joseph Melenhorst,
- Arati S. Desai,
- Arati S. Desai,
- John Y. K. Lee,
- Marcela V. Maus,
- Carl H. June,
- Carl H. June,
- Steven Brem,
- Steven Brem,
- Roddy S. O’Connor,
- Roddy S. O’Connor,
- Zev Binder,
- Zev Binder,
- Donald M. O’Rourke,
- Donald M. O’Rourke
Affiliations
- Joseph S. Durgin
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Joseph S. Durgin
- Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States
- Joseph S. Durgin
- Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Fraser Henderson
- Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, United States
- MacLean P. Nasrallah
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- MacLean P. Nasrallah
- Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Suyash Mohan
- Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Sumei Wang
- Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Simon F. Lacey
- Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States
- Jan Joseph Melenhorst
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Jan Joseph Melenhorst
- Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States
- Jan Joseph Melenhorst
- Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Arati S. Desai
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Arati S. Desai
- Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- John Y. K. Lee
- Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Marcela V. Maus
- Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, United States
- Carl H. June
- Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States
- Carl H. June
- Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Steven Brem
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Steven Brem
- Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Roddy S. O’Connor
- Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States
- Roddy S. O’Connor
- Department of Pathology & Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Zev Binder
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Zev Binder
- Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Donald M. O’Rourke
- Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- Donald M. O’Rourke
- Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
- DOI
- https://doi.org/10.3389/fonc.2021.669071
- Journal volume & issue
-
Vol. 11
Abstract
Autologous chimeric antigen receptor (CAR) T cells targeted to epidermal growth factor receptor variant III (CAR T-EGFRvIII) have been developed and administered experimentally to treat patients with IDH1 wildtype recurrent glioblastoma (rGBM) (NCT02209376). We report the case of a 59-year-old patient who received a single peripheral infusion of CAR T-EGFRvIII cells and survived 36 months after disease recurrence, exceeding expected survival for recurrent glioblastoma. Post-infusion histopathologic analysis of tissue obtained during a second stage surgical resection revealed immunosuppressive adaptive changes in the tumor tissue as well as reduced EGFRvIII expression. Serial brain imaging demonstrated a significant reduction in relative cerebral blood volume (rCBV), a measure strongly associated with tumor proliferative activity, at early time points following CAR T treatment. Notably, CAR T-EGFRvIII cells persisted in her peripheral circulation during 29 months of follow-up, the longest period of CAR T persistence reported in GBM trials to date. These findings in a long-term survivor show that peripherally administered CAR T-EGFRvIII cells can persist for years in the circulation and suggest that this cell therapy approach could be optimized to achieve broader efficacy in recurrent GBM patients.
Keywords
- CAR T cell therapy
- glioblastoma
- EGFRvIII
- recurrent glioblastoma (rGBM)
- CAR (chimeric antigen receptor)
- perfusion imaging
