EXTH-73. A NOVEL ANTI-GALECTIN-3 MONOCLONAL ANTIBODY THERAPEUTIC DIMINISHES MIGRATION AND SLOWS TUMOR GROWTH TO PROLONG SURVIVAL IN GLIOBLASTOMA

Abstract

Abstract Glioblastoma (GBM) is the most aggressive, invasive, and malignant primary brain cancer with a standard of care that hasn’t been improved in over 15 years. Heterogenous tumor cell populations that evade resection and develop resistance to chemoradiation highlight the need for novel therapies that can target both the migratory and proliferative nature of GBM cells. Galectin-3, a carbohydrate-binding protein overexpressed in the GBM parenchyma and stromal astrocytes and microglia/macrophages, is a potent modulator of cell proliferation, migration, angiogenesis, T-cell inhibition, and M2 macrophage polarization. Increased Galectin-3 expression levels correlate to lower survival in glioma patients, and these levels further increase following exposure to temozolomide or radiation alone or in combination, thus more greatly emphasizing the need to target Galectin-3 in GBM patients following initial standard-of-care treatment. Here, we characterize the therapeutic effects of a monoclonal anti-Galectin-3 antibody (Gal3 Ab) we have developed for its ability to inhibit GBM tumorigenic and metastatic potential in several in vitro assays and in vivo heterotopic and orthotopic mouse models. We find that Galectin-3 directly binds to EGFR, the most commonly amplified gene locus in GBM affecting roughly 40% of patients, and our Gal3 Ab can block this binding. Human GBM cells treated with Gal3 Ab show a significant decrease in migration and invasion and reduction in EGFR activation in vitro. In vivo, the Gal3 Ab additionally decreases tumor burden and provides a survival benefit in combination with temozolomide compared to the current standard-of-care treatment alone. Our studies indicate the potential for our novel anti-Galectin-3 antibody to further benefit GBM patients receiving chemoradiation treatment by diminishing tumor cell migration and slowing tumor growth.