gdTCR-Ligand · Investigating the recognition of a novel ligand by gamma-delta T cells and the translation of this interaction into molecules for future cancer immunotherapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-06-01 → 2019-05-31
- EU contribution
- €177,599
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Investigating the recognition of a novel ligand by gamma-delta T cells and the translation of this interaction into molecules for future cancer immunotherapy
Gamma-delta (gd-)T cells are a fast acting subset of T cells that recognize a wide variety of ligands. In contrast to alpha-beta T cells they are not restricted to classical peptide-MHC (pMHC) antigens and the consensus in the field is that they do not interact with pMHC at all. Our preliminary data on a gd-T cell clone shows selective recognition of HLA-A*24:02 positive tumour cells in a pMHC restricted manner, whereas healthy HLA-A*24:02 cells are not recognized. The objectives of this action are; 1) elucidating the molecular mechanism of the gd-T cell receptor (TCR) recognizing pMHC on cancer cells and 2) generating soluble gamma-delta TCR based molecules as therapeutic agents to target cancer cells. Understanding the molecular mechanism of the interaction of gd-TCR with its ligand on the tumor cell surface might open new therapeutic opportunities that haven't been explored thus far. One of these novel opportunities might be the soluble gamma-delta TCR based molecules for immune therapy against cancer.
Data: CORDIS, © European Union
Project objective
Gamma-delta (gd-)T cells are a fast acting subset of T cells that recognize a wide variety of ligands. In contrast to alpha-beta T cells they are not restricted to classical peptide-MHC antigens. Our preliminary data on a gd-T cell clone shows selective recognition of tumour cells mediated through a novel ligand.The aims of this action are; 1) elucidating the molecular mechanism of the gd-T cell receptor (TCR) recognizing the novel ligand on cancer cells and 2) generating therapeutic agents for cancer cells.A multidisciplinary approach will be used to unveil the interaction of the gd-TCR with its ligand. The gd-TCR and novel ligand molecules will be made using recombinant expression. These proteins will be used to characterize this interaction in detail by determining the affinity and the crystal structure. The results generated in this part of the action will increase the current knowledge regarding gd-T cell ligands.The researcher will reintegrate in his home country using his skills in structural immunology, which he acquired in the Rossjohn laboratory at Monash University in Australia, to address the molecular mechanism of the gd-TCR ligand interaction. Additionally, he will be trained by the host laboratory in in vitro and in vivo immunological assays.
Original text from CORDIS.
Participants
- UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtCoordinatorNetherlands
Links
- View on CORDIS
- DOI: 10.3030/749010
- http://www.tumor-immunology-utrecht.nl/news/2017/3/9/eu-grant-for-dennis-beringer-group-kuball
Data: CORDIS, © European Union