Douglas McNeel, MD, PhD, professor, Hematology, Medical Oncology and Palliative Care, has been awarded $1.7M over five years from the National Institutes of Health-National Cancer Institute for a proposal entitled "Improved Anti-Tumor Vaccination – Targeting Checkpoint Regulation at the Time of T-cell Activation."
Dr. McNeel's research group is developing vaccines designed to train the body's own immune system to attack prostate cancer cells. In this NIH-funded research study, scientists will build on their previous work to try to increase the effectiveness of vaccine-initiated prostate cancer immunotherapy.
Normally, the immune system distinguishes between normal cells and cells perceived as "foreign" using checkpoint molecules, which are proteins on certain immune cells that need to be activated or inactivated in order to start an immune response. Certain types of cancer cells exploit this system by using checkpoint proteins to evade being attacked by the immune system.
The checkpoint protein PD-1 acts as an "off switch" on immune cells called T cells, keeping them from attacking other cells in the body. The checkpoint protein LAG-3 is a receptor expressed on activated T cells (as well as other immune cells) that regulates immune responses in cancer. Dr. McNeel and his team had previously shown that PD-1 and LAG-3 are up-regulated after immunization with a prostate cancer anti-tumor DNA vaccine, and this up-regulation of PD-1 and LAG-3 weakens the effectiveness of the vaccine. As a result, the vaccine is less effective at mounting an immune system response to attack prostate cancer cells.
The study is focused on finding ways to block the transient up-regulation of regulatory T cell markers including PD-1 and/or LAG-3 to promote greater anti-tumor activity of prostate cancer DNA vaccines.