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Monday, November 26th, 2018
Centre de Recherche - Paris - Amphithéâtre Constant-Burg - 12 rue Lhomond, Paris 5e

DNA vaccines as treatment for human prostate cancer – targeting the PD-1/PD-L1 pathway as a major mechanism of resistance

Prostate cancer has been viewed as an immunologically “cold” tumor, devoid of large numbers of tumor-infiltrating lymphocytes.  We have been interested in vaccines as T-cell activating therapies to ideally augment tumor-specific cytolytic CD8+ T cells as a treatment for early recurrent prostate cancer.  We have focused on DNA vaccines and on their mechanisms of action to improve the immune response to antigens encoded by DNA vaccines.  In murine studies we found that changes to epitopes encoded by DNA, engineered to increase binding to MHC class I, led to increases in expression of PD-1 on antigen-specific CD8+ T cells that negatively affected anti-tumor response.  Interference with the expression or function of PD-1 at the time of T-cell activation with vaccination led to improved anti-tumor immunity.  These findings, and translation to human trials, will be discussed.  



Douglas McNeel
M.D. Ph.D., Associate Professor

Department of Medicine, division of Hematology/Oncology, University of Wisconsin-Madison (USA)

Invited by

Sebastian Amigorena
Domain 3 - U932 - Immunity and Cancer

Institut Curie


Elodie Mieville

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Douglas G. McNeel, M.D. Ph.D. is currently Associate Professor in the Department of Medicine, division of Hematology/Oncology, at the University of Wisconsin-Madison.  Dr. McNeel received his BA in Chemistry and Music at Whitman College in 1986.  He then pursued graduate training under a Medical Scientist Training Award at the University of Chicago, and received his PhD (Biochemistry and Molecular Biology) in 1992 and MD in 1994. His PhD studies were in the laboratory of Fuyuhiko Tamanoi, PhD.  He then completed an Internal Medicine residency at the University of Washington on a Clinical Investigator Pathway, and a Medical Oncology fellowship at the University of Washington and Fred Hutchinson Cancer Research Center.  After his clinical fellowship training, he joined the Tumor Vaccine Group at the University of Washington in the laboratory of Mary (Nora) Disis, MD for four years as a postdoctoral fellow and junior faculty member, prior to moving to the University of Wisconsin-Madison in 2001.  Dr. McNeel is a genitourinary oncologist with a clinical research focus on immune-based therapies for prostate cancer, and T-cell vaccines in particular.  He serves as co-leader of the Experimental Therapeutics Program of the University of Wisconsin Carbone Cancer Center.  Dr. McNeel has served as PI or study chair for multiple clinical trials, and co-investigator for multiple other trials for patients with genitourinary malignancies.  He serves as PI for a training grant, the goal of which is to train academic physician scientists and provide them protected laboratory research training time.  Dr. McNeel himself has mentored nearly 30 graduate or post-graduate trainees in the laboratory, and many other medical trainees in clinical medicine and clinical research projects.  He is a member of the American Association for Cancer Research, American Association of Immunologists, American Society of Clinical Oncologists, and the Society for Immunotherapy of Cancer.  Dr. McNeel’s laboratory and clinical research program is focused on prostate cancer immunology with the goal of developing anti-tumor vaccines as treatments for prostate cancer.  This work has been supported by multiple extramural grants from the National Institutes of Health and the Department of Defense Prostate Cancer Research Program.