Abstract IA010: Engineering human sialidase as novel cancer therapeutics by targeting sialoglycans

Abstract

Abstract Immune checkpoint blockade has revolutionized cancer treatment, but resistance remains a significant hurdle for many patients. Sialoglycans, as new immune checkpoints on tumors, present a promising therapeutic opportunity to enhance immune response. Cleaving off sialoglycans from tumors using a tumor-associated antigen (TAA) targeted antibody-bacterial sialidase conjugate has shown antitumor activity in preclinical models. Recognizing the immunogenicity risk of bacterial enzymes, we've engineered a human sialidase for therapeutic development. By investigating the roles of sialoglycans on immune cells, we've found that cleaving T cell surface sialoglycans boosts antitumor immunity. Additionally, we've demonstrated the efficacy and tolerability of the untargeted engineered human sialidase Fc fusion (Bi-Sialidase) as a potential immunotherapy. These advancements have led to the development of the EAGLE (enzyme antibody glycan editing) technology platform, which restores antitumor immunity by stripping sialic acids from immunosuppressive sialoglycans on both tumor and immune cells. Citation Format: Li Peng. Engineering human sialidase as novel cancer therapeutics by targeting sialoglycans [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr IA010.