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
• immune checkpoint
• pd-1
• sialic acid
• Siglec

Article highlights

• Changes in glycosylation in tumors have been extensively reported and are often associated with poor prognosis and reduced survival.

• Glyco-immune checkpoints are glycan-binding receptors that can modulate immune responses.

• Targeting glyco-immune checkpoints can promote anti-tumor immunity.

• Treatment approaches targeting glyco-immune checkpoints show promising results in several pre-clinical and clinical studies.

This box summarizes key points contained in the article.

Declaration of interest

H Läubli received travel grants and consultant fees from Bristol Myers Squibb (BMS) and Merck, Sharp and Dohme. H Läubli received research support from BMS, Palleon Pharmaceuticals, and Limmatech Biologics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose

Additional information

Funding

This work was supported by funding from the Goldschmidt-Jacobson Foundation, the Swiss National Science Foundation (SNSF grant #310030-184720), the Schoenmakers-Müller Foundation, an Innosuisse grant and the Cancer League of Basel (KlbB).