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.
M.D. Ph.D., Associate Professor in the Department of Medicine, University of Wisconsin-Madison (USA)
Domain 3 - U932 - Immunity and Cancer