Abstract B035: Antibody-lectin chimeras for glyco-immune checkpoint blockade

Abstract Checkpoint blockade immunotherapy has been a revolution in the treatment of cancer, yet despite its curative potential, most patients remain unresponsive to existing treatments. Altered cell surface glycosylation is a universal hallmark of cancer, associated with poor disease outcomes and increased aggressiveness. Glycans on the surface of tumours engage inhibitory receptors on immune cells, facilitating cancer’s evasion of the immune response. These ‘glyco-immune checkpoints’ – interactions of cell-surface glycans with glycan-binding immunoreceptors known as lectins – have emerged as prominent mechanisms of immune evasion and therapeutic resistance in cancer. Here, we describe antibody-lectin chimeras (AbLecs), a modular platform for glyco-immune checkpoint blockade. AbLecs are bispecific antibody-like molecules comprising a cell-targeting antibody domain and a lectin “decoy receptor” domain that directly binds glycans and blocks their ability to engage inhibitory lectin receptors, preventing immune suppression by the tumour. AbLecs potentiate anti-cancer immune responses in vitro and in vivo, outperforming most existing therapies and combinations tested. AbLecs can be readily designed to target numerous tumour and immune cell subsets as well as glyco-immune checkpoints, and therefore represent a new modality for cancer immunotherapy. Citation Format: Megan J. Priestley, Jessica C. Stark. Antibody-lectin chimeras for glyco-immune checkpoint blockade [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B035.