Combination Therapy Prostate Cancer Vaccine Trial Begins

Dr. Douglass McNeelA clinical trial of a prostate cancer vaccine in combination with a PD-1 blockade drug called pembrolizumab has begun. The strategy of the trial has been informed by a recent proof-of-principal publication by the research team of Douglas McNeel, MD, PhD, professor, Hematology, Medical Oncology and Palliative Care. The authors hope that the combination therapy, if successful in humans, will provide a new approach for improving the effectiveness of cancer immunotherapy regimens.
The general concept behind cancer vaccines is to train the body’s immune system to recognize and destroy tumor cells expressing specific target “antigens.” However, to date, effectiveness in clinical trials has been mixed and tumor immunologists have sought ways to improve success. 
Research published by Dr. McNeel and colleagues, which appeared in the journal Cancer Immunology Research, found that when an optimized prostate cancer vaccine engineered to be highly immunogenic was used in a novel mouse model, it had a surprisingly poor antitumor response compared to the original, non-optimized vaccine. The optimized vaccine caused increased expression of PD-1 (Protein Cell Death-1) on antigen-specific CD8+ T-cells. This increased PD-1 expression was counter-productive, because PD-1 is an immune checkpoint protein that prevents the activation of T-cells. In essence, creating a more immunogenic cancer vaccine resulted in the unintended consequence of causing the elicited T-cells to be less effective at mounting an antitumor response. However, in the mouse study, administering the optimized vaccine in combination with a PD-1 blockade drug increased its effectiveness.
“We’ve been looking for ways to improve the immune response, and we’re hopeful that by combining the vaccine with a PD-1 inhibitor, we’ll increase the efficacy of the vaccine,’’ said Dr. McNeel.
The clinical trial combines a DNA vaccine called MVI-816 with a PD-1 blockade drug called pembrolizumab to see if the regimen can slow the growth of prostate cancer in men with advanced disease. The MVI-816 vaccine is made by Madison Vaccines Inc., which Dr. McNeel helped found. The company is supporting the trial, along with a grant from the Prostate Cancer Foundation. The identifier is NCT02499835 and the trial is currently recruiting participants.
The research leading to this trial has been supported by grants from the U.S. Army Medical Research and Material Command Prostate Cancer Research Program, the National Institutes of Health, and the Prostate Cancer Foundation.