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

Abstract

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis antigens, and polysialic acid. In this review, we analyze strategies for cancer immunotherapy targeting TACAs, including different antibody developments, the production of vaccines, and the generation of CAR-T cells. Some approaches have been approved for clinical use, such as anti-GD2 antibodies. Moreover, in terms of the antitumor mechanisms against different TACAs, we show results of selected clinical trials, considering the horizons that have opened up as a result of recent developments in technologies used for cancer control.

Novel lectin-based chimeric antigen receptors target Gb3-positive tumour cells

“…Our approach serves as proof of concept for developing specific lectin-CARs targeting other tumour-associated carbohydrate antigens. Moreover, targeting of TACAs could be relevant in combinatorial therapies, as they target glycans on the cell surface or in the tumour vasculature, thus, facilitating or enhancing the anti-cancer activity of other immunotherapeutics or drugs as it has been carried out with therapies targeting GD2 and MUC1 [ 91 , 92 ].…”

Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications

“…Scientists have studied the prospect of producing multi-epitopic cancer vaccines that target multiple cell populations in light of the link between various TACA and tumor progression. As a consequence, the same research team revised the vaccination to contain five carbohydrate antigens associated with the advancement of prostate and breast cancer, Globo-H, TF, GM2, TF, STn, and Tn [ 118 ]. A three-component vaccination based on a TLR2 agonist, a T helper epitope, and a tumor-associated glycopeptide (TACA) elicited high titers of IgG antibodies specific for TACA in a similar experiment by another group [ 17 , 115 ].…”

“…To make an anti-cancer vaccine with higher immunogenicity, scientists used click-chemistry for solid-phase synthesis of MUC1 glycopeptide and Pam(3) Cys lipopeptide [ 121 ]. There were many other vaccinations that were extremely effective in killing cancer cells and generating an immunogenic response, such as synthetic glycan vaccines [ 118 ]. Tumor size decreased after immunization with many of these synthetic vaccines in vivo.…”

Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma

“…Indeed, a glycoproteomic fingerprinting would be of great interest to in depth characterize the ECM components to unveil biological mechanisms aiding cell growth and metastatic spreading that could be useful as potential therapeutic targets [ 74 , 102 ].…”