Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer
Abstract
This proposal addresses the Fiscal Year 2014 (FY14) Peer Reviewed Cancer Research Program (PRCRP) Topic Area of Kidney Cancer. The successful treatment for kidney cancer is in the interest of our men and women in uniform and our proposal therefore qualifies for the FY14 PRCRP Military Relevance Focus Area. The number of treatments for kidney cancer has significantly increased over the past 10 years. However, they have one thing in common -- they do not cure kidney cancer. Fortunately, an era of modern immunotherapy has arrived. It is now recognized that tumors actively dampen or turn off an immune response. They do that by using the major breaks of the immune system, called immune checkpoints. Inhibitors of these breaks, for example, antibodies against a molecule on immune cells called programmed-death 1 (PD1), have led to long-term survivors with kidney cancer. Unfortunately, not every kidney cancer patient responds to these treatments, only 10%-20% do, which is just too low. Critically, immune checkpoint inhibitors, such as antibodies targeting the PD1 pathway, do require an ongoing immune response. If the tumor is invisible to the immune system, then these drugs cannot work. Thus, an important strategy to improve response rates is to make these visible and induce an initial immune response. Although vaccines could be used, they may not represent what a patient s tumor "looks like" molecularly. A different approach is to pursue "auto-vaccination." This approach destroys or inflames one of the patient s own tumors, making it visible to the immune system and then maximizes the immune response with PD1 inhibitors. To this end, we will develop cutting-edge strategies to induce immune responses in a relevant mouse model of kidney cancer. We will use radiation, freezing, and pro-inflammatory molecules in a systematic manner to achieve this goal. Importantly, these approaches are highly translatable into the clinic and could truly save kidney cancer patients lives in the short and medium time range.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510141
Entities
People
- Hans-joerg Hammers
Organizations
- Johns Hopkins University
- United States Army