Emerging glyco‐based strategies to steer immune responses

Abstract

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell–cell communications and in the regulation of immune responses. Through the interaction with glycan‐binding receptors, glycans are able to affect the activation status of antigen‐presenting cells, leading either to induction of pro‐inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco‐chemists and glyco‐immunologists to develop glycan‐based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan‐modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen‐presenting cells, like dendritic cells. In addition, we address how glycan‐based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan‐based therapies, including chimeric antigen receptor (CAR)‐T cells to achieve targeting of tumor‐associated glycan‐specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity.

Modified E2 glycoprotein of hepatitis C virus enhances pro-inflammatory cytokines and protective immune response in mice

“…Glycosylation has a role in adaptive immune activation ( 33 ). Appropriate glycosylation of antigens is exploited for the development of more efficacious prophylactic as well as therapeutic vaccines ( 34 ).…”

Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

“…It is noteworthy that human Ramos B-cells carrying V-domain glycosylated B-cell receptors (compared to their non-glycosylated counterparts) undergo increased signaling after stimulation [ 93 ]. Furthermore, glycan-based nanoparticles recently have been used to boost the immune system [ 94 ].…”

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives

“…In parallel, TACAs can interact with antigen-presenting cells through their interaction with glycan-binding receptors (such as SIGLECs, MGL, DC-SIGN), thus inducing immunosuppressive signals [14]. Based on these observations, several strategies using glycan-modified nanoparticles have been developed to improve antitumor immune responses [15]. Deeper knowledge of the structural and functional features of TACAs drives rational drug design, as well as novel antitumor immunotherapy strategies.…”