The new study was born of an interdisciplinary collaboration: neurosurgeons, neuro-oncologists, neuropathologists, immunologists, and transfusion medicine experts have all played key roles in developing the investigational therapy. Penn is the first institution to open a trial utilizing this type of CAR T cell therapy for glioblastoma, and a second study site is now open at the University of California, San Francisco.

The phase I trial will include a total of 12 adult patients whose tumors express EGFRvIII.


After some of each patient's T cells are removed via an apheresis process similar to dialysis, the cells are engineered using a viral vector that programs them to hunt for cancer cells that express EGFRvIII. Then, the new cells are infused back into the patient's bodies, where a signaling domain built into the CAR promotes rapid growth of these cells, building an army of tumor-killing cells that have been shown in studies of blood cancer patients to persist in the body. The investigators believe the cells may then serve as a vaccine-like protection against tumor recurrence.

More than 22,000 Americans are diagnosed with GBM each year. Patients whose tumors express the EGFRvIII mutation tend to have more aggressive cancers: Their tumors are less likely to respond to standard therapies.

"We now need to see in the next set of patients if we can augment the effects of the CAR infiltration into the brain and determine optimal timing and combination of this therapy with other established therapies," O'Rourke said. "In this manner, we believe this highly personalized T cell therapy will begin to show clinical efficacy in a reproducible manner with all patients containing EGFRvIII-positive GBMs."

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Penn co-authors include MacLean P. Nasrallah, Jennifer Morrissette, Jan J. Melenhorst, Simon F. Lacey, Maria Martinez-Lage, Arati Desai, Steven Brem, Eileen Maloney, Suyash Mohan, Sumei Wang, Gaurav Verma, Jean-Marc Navenot, Zhaohui Zheng, Bruce L. Levine, and Carl H. June. Other authors include Keith Mansfield, Randi Isaacs, Jennifer Brogdon and Angela Shen, from Novartis, and Hideho Okada from University of California, San Francisco.

The clinical trial is sponsored by Novartis. In 2012, the University of Pennsylvania and Novartis announced an exclusive global research and licensing agreement to further study and commercialize novel cellular immunotherapies using CAR technologies.

For more information about the glioblastoma trial, visit clinicaltrials.gov.

Editor's Note: Some of the scientists at the University of Pennsylvania and Novartis are inventors of these technologies, and the University as well as the inventors may benefit financially from this work in the future.

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