Targeting glyco-immune checkpoints for cancer therapy

Abstract

Introduction: Targeting immune checkpoints with antibodies has significantly improved the outcome of cancer patients, but only few patients have long-term benefits from currently used PD-1/PD-L1 and CTLA-4 inhibitors. New approaches are needed to increase the number of patients going into long-term remission after cancer immunotherapy. Glyco-immune checkpoints are new targets for cancer immunotherapy. They are defined as immune-modulatory pathways including interactions of glycans with glycan-binding proteins or lectins. The most prominent pathway is the sialoglycan-Siglec axis and inhibitors of this axis are already successfully tested in early clinical trials.Area covered: Here, we summarize the current knowledge on glyco-immune checkpoints with a focus on the sialoglycan-Siglec axis. We also provide an overview on current approaches to clinically target glyco-immune checkpoints and give an outlook for the further clinical development of glyco-immune checkpoint targeting agents.Expert opinion: Glyco-immune checkpoints are interesting new targets to improve cancer immunotherapy. Antibodies targeting the sialoglycan-Siglec axis are already in clinical development. Other approaches with higher risk of toxicity including tumor-targeted sialidases are in late stage pre-clinical development. Despite the challenges, targeting of glyco-immune checkpoints could lead to the development of a new class of drugs providing improved anti-cancer immunity and eventually benefit cancer patients.

Keywords: Galectin; Siglec; immune checkpoint; pd-1; sialic acid.