Unravelling the CTLA-4 immune checkpoint: from cell biology to clinical application. (360G-Wellcome-204798_Z_16_Z)

£1,653,759

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