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PhD in Immunology and Immunotherapy: Characterising the molecular interactions between the CTLA-4 and PD1 pathways

  • Full or part time
  • Application Deadline
    Friday, March 20, 2020
  • Funded PhD Project (UK Students Only)
    Funded PhD Project (UK Students Only)

Project Description

Immunotherapy has revolutionised the treatment of cancer. The 2018 Nobel Prize in medicine to Allison and Honjo recognised this groundbreaking shift in our approach to cancer treatment whereby instead of cytotoxic drugs targeting cancer tissue, antibodies are used to remove the “brakes” on the immune system. This targeting of the immune system and not the cancer represents a fundamental change in thinking, recognising that cancer can be targeted by the immune system and therefore manipulating the immune response can be highly beneficial.

The two main checkpoints targeted to date have been the CTLA-4 and PD-1 pathways, which have been targeted both separately and increasingly together. It is now emerging that there are newly identified physical interactions between these pathways at the molecular level which have yet to be properly characterised.

The Sansom lab identified that CTLA-4 has the remarkable ability to capture and destroy its ligands (CD80 and CD86) using a cell biological process known as Transendocytosis (TE). Recent data has also revealed that one of the CTLA-4 ligands (CD80) also directly interacts with a ligand from the PD-1 pathway (PD-L1) and we will explore the impact of TE on this interaction.

The proposed project will therefore explore new strategies for manipulating these interactions in a collaboration between the Sansom lab at UCL and the Dovedi lab at Astra Zeneca. The project will provide a focused training on the molecular and cellular biology of these immune checkpoints as well as direct experience of the pharmaceutical industry relating to antibody based therapeutics.

Informal enquiries can be made by email to

Funding Notes

Fully funded place including home (UK) tuition fees and a tax-free stipend in the region of £17,009. Students from the EU are welcome to submit an application for funding, any offers will be subject to MRC approval and criteria.

References

Qureshi et. al., Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4 Science 2011: 332, 600-603
Sansom DM and Walker LSK. Dimers aren’t forever: CD80 breaks up with PD-L1. Immunity 2019: 51, 972-974

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