Utilizing the Immune Response to Tumor Neoantigens for Kidney Cancer Early Detection
Abstract
Background and Objectives: The 5-year survival for stage I renal cell carcinoma (RCC) is 95% whereas for stage IV RCC, the 5-year survival is 19%. Unfortunately, approximately 30% of RCC patients are still diagnosed with locally advanced RCC or distant metastases (stage IV) at first presentation. There is no established screening test for RCC. We will determine if antibody profiling from blood has potential to detect RCC. In this project, we propose to use a novel technology, Serum Epitope Repertoire Analysis (SERA) (Serimmune Inc.), to profile the antibody landscape in RCC and investigate the utility of antibodies as biomarkers for RCC early detection. We hypothesize that the presence of stage I RCC results in a detectable antibody signature, and that the signature can distinguish indolent, low-grade RCC from more aggressive, high-grade RCC. Study Design: We will first profile the antibody signatures in blood from 200 patients with RCC and benign kidney lesions, using the SERA platform. First, we will determine if antibody signatures can distinguish RCC blood from 800 matched healthy controls. Then we will determine if antibody signatures can distinguish low-grade from high-grade RCC. We will then test the signatures in independent test sets. Innovation: The highly novel SERA platform, which is accessible to us through a collaboration with Serimmune, is one of the largest peptide libraries available to detect antibodies in blood. Impact: Patients with advanced or metastatic RCC require costly systemic treatments to control their cancer (estimates as high as $5.2 billion per year in the U.S. in 2011 and increasing ever since). Patients suffer from decreased quality of life due to cancer symptoms and treatment side effects. Despite advances in targeted therapy, almost all metastatic RCC patients ultimately succumb to disease progression. The dramatically decreased life expectancy of patients with mRCC and the physical and financial toxicity of treatment highlight the need for better cure rates through early detection. A blood-based antibody assay could change clinical practice in the detection and management of RCC. A minimally invasive screening test that identifies RCC in combination with a diagnostic blood test that helps avoid surgery, and thus overtreatment of clinically insignificant renal lesions, would be a big step forward towards precision early detection of RCC. Lastly, if we find an antibody signature that is detectable for small RCC lesions, the signature may be used to detect recurrence, or response to therapy in advanced disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110269
Entities
People
- Alice Fan
Organizations
- Stanford University
- United States Army