Abstract 1146: A novel anti-Galectin-3 antibody therapeutic for the treatment of glioblastoma

Abstract

Abstract Characterized by rapid growth and diffusely infiltrative spread, glioblastoma (GBM) is the most common and most malignant primary brain cancer with a very poor prognosis and a standard of care that hasn’t been improved in over 15 years. The need for new therapies that can directly or indirectly target heterogeneous tumor cell populations to inhibit cell migration in addition to proliferation is highlighted by the recent efforts to develop targeted therapies to treat the vast majority of GBM patients whose tumors impede gross-total resection and develop resistance to chemoradiation. Galectin-3, a carbohydrate-binding protein overexpressed in astrocytes, microglia/macrophages, and the stroma of GBM tumors is a potent modulator of cell proliferation, migration, angiogenesis, T-cell inhibition, and M2 macrophage polarization. We and others have confirmed the association of Galectin-3 expression to lower survival in glioma patients. Additionally, tumor Galectin-3 levels have been shown to increase following exposure to temozolomide or radiation alone or in combination, thus more greatly increasing the need for targeting Galectin-3 in GBM patients following initial treatment. Here, we characterize the therapeutic effects of the anti-Galectin-3 antibody (Gal3 Ab) we have developed for the ability to inhibit GBM tumorigenic and metastatic potential in several in vitro assays and in vivo in heterotopic and orthotopic mouse models. Human GBM cells treated with Gal3 Ab show a significant decrease in cell viability, migration, and invasion in vitro. In vivo, the Gal3 Ab 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 to be added to the very limited arsenal of potential treatments for GBM. Citation Format: ANNE MARIE BARRETTE, Krutika Deshpande, Marvin Cadiente, Anji Bei, Xi Wang, Teodelinda Mirabella, Dongxu Sun. A novel anti-Galectin-3 antibody therapeutic for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1146.