Glycomaterials for immunomodulation, immunotherapy, and infection prophylaxis

Abstract

Synthetic materials that can engage the innate and adaptive immune systems are receiving increasing interest to confer protection against onset of future disease, such as pathogen infection, as well as to treat established diseases, such as autoimmunity and cancer. Carbohydrates are integral to various immune-related processes, including inflammation, adaptive memory, and tolerance, through both their non-covalent recognition of carbohydrate-binding proteins and as chemical signatures that distinguish self from non-self. Harnessing the biological activity of carbohydrates, however, was long hindered by the lack of a ‘sugar code’ defining their structure–function relationships, the difficulty of carbohydrate synthesis, and the weak binding affinity of monovalent carbohydrates for proteins or other biomolecules. The advent of new glycan synthesis approaches, combined with increased understanding of the role of multivalent carbohydrate clusters in immunology, has spurred significant recent growth in the development of multivalent synthetic materials modified with carbohydrates (i.e. “glycomaterials”) to activate, temper, or inhibit specific immunological processes. In this review, we highlight recent advances in glycomaterials that can inhibit T cell apoptosis, establish antigen-specific tolerance, suppress inflammation, or inhibit viral entry into host cells via non-covalent recognition of carbohydrate-binding proteins. In addition, we survey glycomaterials that can act as vaccines for adaptive immunological recognition and memory of carbohydrate antigens, with a particular emphasis on vaccines against tumor-associated carbohydrate antigens as cancer immunotherapies. In total, these examples demonstrate the enormous potential of glycomaterials to prevent or treat diverse diseases by engaging specific immunological processes.