Prognostic and Predictive Markers of Immunogenicity in Renal Cell Carcinoma
Abstract
Hypothesis to be tested and the scientific objective and rationale: We hypothesize that mutations in genes that regulate and control our chromosomes, called chromatin remodeling genes, modify how kidney cancer cells influence their immediate surroundings by altering the expression of genes that attract, repel, or inactivate immune cells. The changes caused by these genes may specifically change how the immune system can attack tumors. These changes will also alter how patients respond to the new checkpoint antibody immune therapies. Understanding how these changes modify the immune system will help us identify which patients are most likely to respond to checkpoint antibody immune therapy and will help us develop new treatments to overcome resistance to checkpoint therapy in nonresponding patients. We will achieve our objectives by analyzing the relationship between mutations in chromatin remodeling genes, the degree and type of immune infiltrates, and the response to immune therapy. We will then “look under the hood” of the cancer cells themselves and define the precise mechanism by which mutations in chromatin remodeling genes alter the expression of factors that modulate the immune system and test these findings in an animal model system. We will then determine in an animal model whether and under which genetic conditions the combination of checkpoint therapy and checkpoint therapy can augment response, which will position us to verify these findings in patients. Ultimate applicability of the research: What types of patients will it help and how? This research will help all patients with metastatic kidney cancer, including military personnel, Veterans, and the general public. It will help them by allowing us to identify which patients are most likely to benefit from checkpoint therapy and to help develop new ways to overcome resistance to therapy in patients who do not respond to these new therapies. What are the potential clinical applications, benefits and risks? This research will be immediately applicable to individuals with metastatic kidney cancer who are considering treatment options. There are clear benefits to patients. The only risk is if our predictive marker becomes widely used and is not highly accurate; it may skew treatment decisions by doctors. We will safeguard against that by validating our findings with future confirmatory studies. What is the projected time it may take to achieve a patient-related outcome? By the end of this 3-year project, we will be in a position to perform confirmatory studies of our findings on patients. What are the likely contributions of this study to advancing one of the Fiscal Year 2016 Peer Reviewed Cancer Research Program Topic Areas? This research will for the first time provide predictive biomarkers for patients with kidney cancer receiving immune therapy. How the proposed research will benefit Service members, their families, Veterans, and/or other military beneficiaries: This research will directly affect Service members, their families, Veterans, and/or other military beneficiaries who are afflicted with kidney cancer. It will help select the right therapy for them and will aid in developing better alternative treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710307
Entities
People
- Eric Jonasch
Organizations
- United States Army
- University of Texas at Austin