Summary
The appearance of aberrant glycans on the tumor cell surface is one of the emerging hallmarks of cancer. Tumor growth is accompanied by tumor evasion of the immune system which limits the efficacy of cancer vaccines. However, and despite the fact that aberrant tumor glycosylation alters how the immune system perceives the tumor and, can also induce immunosuppressive signaling through glycan-binding receptors, the role of tumor glycosylation in immune evasion has mostly been overlooked. It is clear that new strategies to avoid the immune escape mechanisms generated by tumor cells are required. The interaction between the immune system and Tumor-Associated Carbohydrates Antigens (TACAs) is facilitated by a diverse set of carbohydrate-binding receptors, as the C-type lectin receptors (CLRs) which mediate specific interactions with TACAs controlling many features of the immune response. The immune escape mechanisms generated by truncated O-glycans, such as Tn antigen (αGalNAc-Ser/Thr) are still poorly understood. Human macrophage galactose-type lectin (hMGL) is a CLR that recognizes terminal GalNAc moieties, and is, therefore, a prime receptor for the aberrant O-glycans in cancer. MGL is upregulated in tolerogenic and immature dendritic cells (DCs) and macrophages playing an important role in immunosuppression. It interacts with effector T-cells, resulting in reduced proliferation, cytokine secretion and induction of T-cell apoptosis. In this project, we propose the design and synthesis of multivalent MGL ligands mimetics with an improved affinity toward this receptor, that will serve as selective inhibitors to reverse GalNAc-mediated immune suppression for cancer immunotherapy.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/840663 |
| Start date: | 01-06-2019 |
| End date: | 08-10-2021 |
| Total budget - Public funding: | 172 932,48 Euro - 172 932,00 Euro |
Cordis data
Original description
The appearance of aberrant glycans on the tumor cell surface is one of the emerging hallmarks of cancer. Tumor growth is accompanied by tumor evasion of the immune system which limits the efficacy of cancer vaccines. However, and despite the fact that aberrant tumor glycosylation alters how the immune system perceives the tumor and, can also induce immunosuppressive signaling through glycan-binding receptors, the role of tumor glycosylation in immune evasion has mostly been overlooked. It is clear that new strategies to avoid the immune escape mechanisms generated by tumor cells are required. The interaction between the immune system and Tumor-Associated Carbohydrates Antigens (TACAs) is facilitated by a diverse set of carbohydrate-binding receptors, as the C-type lectin receptors (CLRs) which mediate specific interactions with TACAs controlling many features of the immune response. The immune escape mechanisms generated by truncated O-glycans, such as Tn antigen (αGalNAc-Ser/Thr) are still poorly understood. Human macrophage galactose-type lectin (hMGL) is a CLR that recognizes terminal GalNAc moieties, and is, therefore, a prime receptor for the aberrant O-glycans in cancer. MGL is upregulated in tolerogenic and immature dendritic cells (DCs) and macrophages playing an important role in immunosuppression. It interacts with effector T-cells, resulting in reduced proliferation, cytokine secretion and induction of T-cell apoptosis. In this project, we propose the design and synthesis of multivalent MGL ligands mimetics with an improved affinity toward this receptor, that will serve as selective inhibitors to reverse GalNAc-mediated immune suppression for cancer immunotherapy.Status
TERMINATEDCall topic
MSCA-IF-2018Update Date
28-04-2024
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