Abstract 1147: A novel anti-Galectin-3 antibody therapeutic for the treatment of triple negative breast cancer

Abstract

Abstract About 43,600 women in the U.S. are expected to die in 2021 from breast cancer. Triple negative breast cancer (TNBC), which accounts for approximately 15% of all breast cancers, is diagnosed by exclusion of expression and/or amplification of three biomarkers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]).Characterized by a high risk of relapse (one half of patients with early stages experience recurrence), short overall survival and progression-free survival (life expectancy of few months after failure of first-line chemotherapy), TNBC represents a high unmet medical need. Galectin-3 plays multiple roles in tumor initiation and development via a variety of cellular processes, spanning from angiogenesis to tumor migration. Galectin-3 (Gal3) expression is induced in TNBC patients and highly correlates with poor survival, as shown by our and others’ bioinformatics analysis from public database. We recently discovered and patented a series of antibodies with high specificity and affinity for Gal3, one of which is currently tested in human volunteers. This clinical candidate has shown superior pharmacokinetic properties and clean toxicity profile in GLP studies on non-human primates. Here, we show that anti-Gal3 inhibit both anchorage dependent and independent growth of TNBC cells, as well as Gal3-induced escape from NK cell killing. Also, anti-Gal3 proved to be efficacious in in vivo studies, where TNBC cells were implanted in mammary fat pads of mice and tumor progression, measured as growth of primary mass and presence of metastatic nodules in the lungs, was followed during the two months of treatment. The results presented herein support the conclusion that our therapeutic modality could offer an alternative promising treatment of TNBC. Citation Format: Li Zhang, Heng Wu, Karyssa Palopo, Jie Hu, Marvin Cadiente, Anh Nguyen, Teodelinda Mirabella, Dongxu Sun. A novel anti-Galectin-3 antibody therapeutic for the treatment of triple negative breast cancer [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 1147.