CORDIS
EU research results

CORDIS

English EN
Targeting hMGL-GalNAc interactions to reverse immune suppression in cancer

Targeting hMGL-GalNAc interactions to reverse immune suppression in cancer

Objective

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES- CIC biomaGUNE

Address

Paseo Miramon 182, Parque Tecnologico De San Sebastian Edificio Empresarial C
20009 San Sebastian

Spain

Activity type

Research Organisations

EU Contribution

€ 172 932,48

Project information

Grant agreement ID: 840663

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 172 932,48

  • EU contribution

    € 172 932,48

Coordinated by:

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES- CIC biomaGUNE

Spain