Combining Immunotherapy with Nanoparticles for Improved Kidney Cancer Outcomes
Abstract
Kidney cancer is a common type of cancer that will be diagnosed in close to 64,000 individuals in the US this year. Challenges to treating kidney cancer include the problem that many cancers are not detected until they are at a late stage (which means they cannot be removed by surgery) and that this cancer type is generally resistant to the chemotherapies commonly used to treat other cancers. Targeted therapies inhibit specific molecules that drive cancer growth and have proven useful in treating the most common type of kidney cancer, renal cell carcinoma (RCC), which makes up about 90% of kidney cancers. However, most kidney cancers become resistant to these agents and will progress. Recently, the outlook for people who have kidney cancer has improved due to the development of new drugs that can "awaken" the person’s own immune system to attack the cancer. These new drugs (called immune therapies) can lead to long-lasting cancer control in some kidney cancer patients. Unfortunately, these immune therapies are effective in only about 25% of kidney cancer patients and may stop working after about a year of treatment. Researchers are trying to understand why only some patients benefit from these immune-based therapies and to devise ways to induce additional or longer responses. The goal of our project is to test an idea we have for how to improve the effectiveness of immune therapies for kidney cancer. Our idea, which is based on emerging knowledge about how nanoparticles and the immune system interact, is that certain synthetic nanoparticles (particles that measure around one-millionth of an inch) will boost the effectiveness of immune therapies for kidney cancer. We predict that some types of nanoparticles will convert specific immune cells within the tumor (called macrophages) from a state that blocks the activity of immune therapies to a state that promotes an immune response against the tumor. Various types of nanoparticles are already being used as human medicines and these will be the focus of this research project. We propose to test our idea using cultured immune cells (i.e., macrophage cells grown in a dish outside of the body) and in mice that develop tumors made from kidney cancer cells. To begin, we will test the effects of several types of nanoparticles on the macrophage cells to help us identify which nanoparticles are capable of inducing the conversion to a state that will boost the immune therapies. Those nanoparticles that work well in the initial tests will then be injected into mice to see if they can have the same effects on the macrophage cells within the tumors of these mice. Finally, using the nanoparticles that we find to be most effective at converting the macrophages in mice, we will determine if they can boost the effectiveness of immune therapies using the mouse model of kidney cancer. We can do this by comparing the rate of tumor growth in mice that are treated with immune therapy, nanoparticles, both, or neither. Our project will be the first test of this innovative idea. The proposed research may ultimately have a major impact for Service members, their families, Veterans, and the American public because it could lead to improved kidney cancer treatments that would be available within the next few years. The types of nanoparticles we plan to test are already approved for use in humans, which means that we could move quickly to evaluating our approach in human clinical trials if we are able to find a type that works well in the mouse model of kidney cancer. The ultimate goal of this project is to find a way to stimulate the immune system so that it will attack and destroy the cancer cells in the majority of kidney cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810428
Entities
People
- Paula Bates
Organizations
- United States Army
- University of Louisville