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Complete humanisation of adaptive cellular immunity in the mouse: Vaccine and therapeutic TCR discovery (360G-Wellcome-210525_Z_18_Z)

Adaptive cell mediated immunity is one of the central components of immunological homeostasis. While the basic mechanisms are conserved the components that encounter antigen are subject to rapid evolutionary change driven by species specific pathogens co-evolving with the host and divergence of the host genome against which antigen receptors are negatively selected. Thus, epitopes that direct protective immunological responses differ between species. Consequently, translation of results obtained from immunisations conducted in model organisms to humans remains a pernicious issue. The long term goals of this proposal are to identify and validate vaccine candidates and discover therapeutic T cell receptors To achieve these goals we will build mice in which all components of adaptive cellular immunity have been humanised, building on the technical success, biological insights and health-care benefits accrued from the construction of a mouse with a complete human immunoglobulin repertoire. We will use this humanised mouse as platform to isolate therapeutic T cell receptors for acute myeloid leukaemia in which the nucleophosmin gene has been mutated. In an independent and parallel work stream we will systematically explore the Plasmodium falciparum genome to identify vaccine candidates protective against the liver stage of the pathogen.

£5,000,000

30 Sep 2018

Grant details
Amount Awarded 5000000
Applicant Surname Bradley
Approval Committee Internal Decision Panel
Award Date 2018-09-30T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Strategic Support: Science
Internal ID 210525/Z/18/Z
Lead Applicant Prof Allan Bradley
Planned Dates: End Date 2023-11-01T00:00:00+00:00
Planned Dates: Start Date 2018-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
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