Translational Immunotherapy for Brain Tumors: Bugs, BiTEs, and Oil – Turning Knowledge Into Money

John Sampson
John Sampson
Professor & Chair, Department of Neurosurgery, Duke University
Thursday, October 29, 2015 - 4:30pm
Fitzpatrick Center, Schiciano Auditorium B

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Abstract

Cancer is a disease of mutated DNA. Drug approaches that try to eliminate the downstream effects of these mutations have been ineffective or toxic in combination. In contrast, immunotherapy can effectively target these mutations in protein to specifically eliminate tumor cells without collateral damage to the normal tissues. We have developed several immunotherapy approaches targeting the tumor-specific mutant epidermal growth factor receptor (EGFRvIII) found in > 30% of GBM. Currently, my laboratory is targeting this mutation with bispecific T cell Engagers (a novel EGFRvIII-specific antibody-based molecule) and with a peptide vaccine that has demonstrated a clinically important and statistically significant survival advantage in patients with glioblastoma. Furthermore, the recent discovery by my laboratory and others of the nearly universal presence and homogeneous expression of Cytomegalovirus (CMV) antigens in GBM, but not normal brain, is now well-established and provides an unparalleled opportunity to subvert these viral proteins as tumor-specific targets as well.  Patients with GBM randomized to receive tetanus (Td) as a novel vaccine-site pre-conditioning prior to CMV pp65-loaded DC immunization experienced significantly enhanced PFS and OS in comparison to controls as reported in our recent publication in Nature. Correlative murine studies also demonstrated the enhanced antitumor efficacy of Td preconditioning.The biology behind these vaccines and their commercial development has been licensed and studied in Phase III trials. 

Biography

John Sampson was appointed the first chair of the newly created Department of Neurosurgery at Duke University in 2015. He is a recognized leader in the surgical and experimental treatment of brain tumors with a focus on immunotherapy and drug delivery. He has authored more than 200 peer-reviewed publications which have documented the development of multiple immunotherapeutics which will impact the standard of care in glioblastoma. One of his vaccines was recently licensed to industry, and a worldwide Phase III clinical trial has been completed. This same vaccine, targeting the tumor-specific mutation in the epidermal growth factor receptor (EGFRvIII), demonstrated clear survival advantage in a multi-center randomized Phase II study. Research from his laboratory has been highlighted in major news outlets including the CBS Evening News, ABC, NBC, 60 Minutes, the Associated Press, The Wall Street Journal, and The Diane Rehm show.

He received formal training in medicine, basic science research, clinical trial design and execution, and health sector management and leadership. He did his research training under the internationally renowned scientist, Darell D. Bigner, and Nobel Laureate Gertrude Elion. He currently focuses his clinical practice on treating patients with both benign and malignant brain tumors and divides his time between his clinical practice and an active research laboratory investigating new modalities of direct brain tumor infusion and immunotherapy. He has remained continuously funded by the NIH since completing his residency in neurosurgery.

Dr. Sampson earned his medical degree from the University of Manitoba in Winnipeg. His PhD in pathology and MHSc in clinical research were conferred at Duke University. He also received his MBA from the Duke University Fuqua School of Business. In 2015, Dr. Sampson presented the prestigious Society for Neuro-Oncology (SNO) and the Congress of Neurological Surgeons (CNS) Abhijit Guha Lecture and received the Ronald L. Bittner Award from the American Association of Neurological Surgeons (AANS). These are two of the highest honors bestowed in his profession.