Abstract 2914: ITGA-2 is a novel therapeutic target for glioblastoma and high-grade gliomas

Abstract

Abstract High grade gliomas, including glioblastoma multiforme (GBM), are the most common brain cancers in adults, representing between 15 and 20% of all brain tumors diagnosed, including a significant fraction of pediatric cases. It is also among the most deadly tumor types, with only approximately 5% of diagnosed GBM patients surviving 5 years post-diagnosis. Treatment for this type of tumor involves brain surgery, typically paired with intense chemotherapy and radiation. The ultimate goal of this study is to develop clinically safe, specific, and effective antibody-directed therapeutics for these devastating cancers. Our experimental approach used four established cell lines, consisting of three commercial GBM cell lines (A172, U87, and U118 MG) recommended by the American Type Culture Collection (ATCC) as representative GBM lines, and a control glial cell line (SVGP12) recommended by ATCC as a control. Each of these lines were cultured according to standard protocols and stained, followed by a quantitative and unbiased screening of 72 common cancer targets using comparative flow cytometry. Based on relative immunofluorescence, we found that the cell surface marker integrin alpha-2 (ITGA-2) was elevated thousandfold or more in all three of the tumor lines tested while showing minimal to no expression in the healthy glial control. All assays were conducted in triplicate and confirmed via immunofluorescence staining and confocal fluorescent microscopy. When compared with the currently used molecular target for GBM, Epidermal Growth Factor Receptor (EGFR), ITGA-2 is both more strongly expressed on the three tumor cell lines and significantly less expressed on the healthy glial cells. These data suggest that ITGA-2 demonstrates significantly improved targeting specificity and efficiency potential compare d to EGFR. Potential therapeutic efficacy was also evaluated via antibody blockade. Significantly reduced growth and migration of these tumor cells following ITGA-2 neutralizing antibody blockade was confirmed via standard assays conducted over 24 and 48 hour periods with antibody titration curves. The presence of ITGA-2 was also confirmed in GBM tissue, with its absence noted in healthy brain tissue, via staining of tissue microarrays for ITGA-2. In conclusion, we have discovered a novel cell-surface marker for GBM that is robustly expressed on multiple representative GBM cell lines but not on normal control glial cells. This finding may have significant clinical potential for the treatment of glioblastoma multiforme and other high grade gliomas and supports further research into the use of ITGA-2 as a therapeutic target for GBM. Our ultimate goal is to leverage these findings to develop precision-targeted nanomedicine with the capability to encapsulate and successfully deliver both radiosensitizing agents and chemotherapeutics, providing a novel method to target tumors and improve patient outcomes using tailored therapy. Citation Format: Alexander Moses-Gardner, Peng Guo, Marsha Moses, Edward Smith. ITGA-2 is a novel therapeutic target for glioblastoma and high-grade gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2914.