Abstract 3863: Cancer immunotherapy: Could TK1 be used as a target for colon cancer

Abstract

Abstract The aim of this study is to determine whether Thymidine Kinase 1 (TK1) would be a suitable target for future immunotherapeutic treatment of colon cancer. The salvage pathway enzyme TK1 has been shown to be upregulated in cancer patients due to active proliferation of cancer cells and the resulting high demand for nucleotides. Present in both the cytosol and the serum of cancer patients, TK1 levels can be used to not only predict cancer occurrence, but also to predict tumor aggressiveness and future remission. While serum levels of TK1 have been established, surface expression of the enzyme have not been fully characterized. In colon cancer cells, TK1 has been shown to strongly associate with the plasma membrane. In this project we explored the presence of TK1 on the surface of colon cancer cells (HT29 and SW620 cell lines) using flow cytometry, confocal microscopy, scanning electron microscopy, membrane separation, and cytoplasmic staining. Using fluorescent antibodies conjugated to FITC, expression levels as high as 19% are observed in HT29's and 12% in SW620's in comparison to sodium potassium ATPase surface levels of 11% and 6% respectively. Confocal microscopy images revealed direct overlap between cells stained with a rhodamine red membrane dye and with a FITC conjugated anti-TK1 antibody which indicates a direct relationship between TK1 and the cellular surface of cancer cells. To further confirm surface expression, TK1 levels were assessed using gold labeling and scanning electron microscopy. Gold levels indicate the physical location of the TK1 on the surface of the colon cancer cells and their relative abundance. TK1 surface levels in colon cancer cells corresponded with the surface expression levels of sodium potassium ATPase and share relatively the same abundance. These results strongly indicate a direct relationship between TK1 and the surface of colon cancer cells, and suggests TK1 as a potential target for future immunotherapeutic treatment. Citation Format: Michelle H. Townsend, Evita G. Weagel, Wei Meng, Craig Chandler, Richard A. Robison, Kim L. O’Neill. Cancer immunotherapy: Could TK1 be used as a target for colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3863.