Abstract 205: ELTD1 and Plexin-B2 as novel antibody therapies against glioma biomarkers

Abstract

Abstract PURPOSE: Gliomas consist of up to 80% of malignant brain tumors that are invasive and typically resistant to radiotherapy and chemotherapy. Finding biomarkers to high-grade gliomas can enable better diagnosis and therapeutic intervention for this disease. Through bioinformatics and microarray experiments, we have identified ELTD1 and Plexin-B2 as biomarkers for high-grade human gliomas. Here, we report our findings in vivo using anti-ELTD1 and anti-Plexin-B2 antibodies on mouse GL261 glioma models. Using MRI we investigate tumor growth and animal survival rate, and as well as report histological findings using mouse tumor tissue. METHODS: Mice were implanted with GL261 cells and were either untreated or administered anti-ELTD1, anti-VEGF or anti-c-Met antibodies. MRI experiments were performed on a magnet imaging system. Animals were immobilized by using isoflurane and O2 and placed in a coil for signal transmission. MRI was used to assess tumor growth and calculate tumor volumes over a 21 day time period. Percent survival was obtained from time-points when mice are euthanized 1-2 days prior to expected disease-initiated deaths. Additionally, representative histology slides (H&E) obtained from GL261 glioma-bearing mice that were either untreated (UT) or treated with anti-ELTD1, anti-c-Met, or mouse anti-VEGF antibodies. Histogram of mitotic index and atypical mitosis were identified. Lastly, representative IHC slides for CD-31 obtained from GL261 glioma-bearing mice that were either untreated (UT), or treated with anti-ELTD1, anti-c-Met, or mouse anti-VEGF antibodies to compare MVD (number of vessels/m2) for each group. RESULTS: There was a significance increase in animal survival for anti-ELTD1 and anti-Plexin-B2 and anti-VEGF antibodies when compared to untreated mice. There was a significance decrease in tumor volumes for anti-ELTD1 and anti-Plexin-B2 anti-VEGF and anti-c-Met (***p<0.001) when compared to untreated animals. Significant decreases in the mitotic index were also found for anti-ELTD1 and anti-c-Met treatment groups compared to untreated mice (p<0.05 for both). Significant decreases in MVD were found for the anti- ELTD1 treatment group compared to untreated mice (p<0.01) and finally, anti-ELTD1 therapy also had a significantly decreased MVD compared to anti-c- Met or anti-VEGF therapies. DISCUSSION: ELTD1 is found to be associated with angiogenesis and Plexin-B2 is associated with cell proliferation and angiogenesis. Our in vivo studies have found that anti-ELTD1 and anti-Plexin-B2 antibodies to decrease tumor volumes and increase animal survival in mouse GL261 glioma models. Additionally, anti-ELTD1 therapy was found to decrease the mitotic index and MVD in mouse GL261 glioma model. Future studies will investigate anti-ELTD1 and anti-Plexin-B2 antibody therapies in human xenografts. Our results indicate that anti-ELTD1 and anti-Plexin-B2 antibodies could be potential therapies for high-grade gliomas in humans. Citation Format: Jadith Ziegler, Richard Pody, Landon Rodriguez, Nataliya Smith, Debra Saunders, Patricia Coutinho de Souza, Jonathan Wren, Rheal Towner. ELTD1 and Plexin-B2 as novel antibody therapies against glioma biomarkers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 205. doi:10.1158/1538-7445.AM2015-205