Unravelling the CTLA-4 immune checkpoint: from cell biology to clinical application. (360G-Wellcome-204798_Z_16_Z)
The CTLA-4 pathway is a key immune regulator whose absence or mutation leads to profound autoimmunity. CTLA-4 and its relative CD28 have opposing inhibitory and stimulatory functions respectively and interact with two ligands CD80 and CD86. Despite the key role of this pathway in immune regulation and high profile therapies in tumour immunology, our understanding of how CTLA-4 functionally interacts with its two natural ligands is remarkably incomplete. The aim of this proposal is to generate a robust molecular, cellular and functional framework for CTLA-4 biology which can be used to understand the impact of disease mutations, which are being identified as a result of next generation sequencing programmes, and generate knowledge which can underpin new approaches to manipulation of this key immune axis. We will address three key aims: 1). What is the cellular machinery used by CTLA-4 to capture and transfer ligands between cells? 2). How do CTLA-4 interactions with its natural ligands influence its function? 3). How do clinically identified mutations inform our understanding of the CTLA-4 pathway?
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Grant Details
Amount Awarded | 1653759 |
Applicant Surname | Sansom |
Approval Committee | Science Interview Panel |
Award Date | 2016-11-30T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 204798/Z/16/Z |
Lead Applicant | Prof David Sansom |
Partnership Value | 1653759 |
Planned Dates: End Date | 2024-01-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-02-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |