Decoding antigen specificity of T cells in Ulcerative Colitis

Lead Participant: ORBIT DISCOVERY LTD

Abstract

The immune system plays a key role in a broad range of disease -- including cancer, infection and autoimmunity. In recent years, treatment approaches which modulate the immune system have proved effective in a range of major diseases. T-cells are a key component of the immune system, with the capability of exquisitely recognising diseased or healthy tissue and acting powerfully to eliminate cells and tissues where required. However, altered T-cell responses have also been shown to cause inflammation in certain circumstances.

Ulcerative colitis is an important form of bowel inflammation which carries a major burden on patients and their families. Current treatments are largely inadequate and non-specific and can often be limited by side-effects and risks. Members of the proposed team have shown that T-cells can contribute to the bowel inflammation. However, it is still unclear what triggers the T-cells. This is an important question if we are to find new approaches to treatment.

T-Cypher Bio has developed a powerful approach to discover "antigens" that trigger T-cells and has focussed on developing therapeutics based on the receptors that recognise these antigens for the treatment of cancer. Here, T-Cypher Bio will work with pioneers in the role of T-cells in inflammation and the use of novel single cell technologies, Professor Alison Simmons and Professor Graham Ogg at the University of Oxford. Specifically, samples will be taken from patients with Ulcerative Colitis and controls to define antigens and T-cells using the T-Cypher technology (T-Cypher-seq) and other approaches to examine individual T-cells in the tissue samples. These large patient-derived data-sets will provide the basis to develop therapeutic approaches to control the inflammation. T-Cypher will innovate to increase the types of T-cells which can be examined, allowing access to new inflammatory disease markets. The insights will be directly applicable to inflammatory bowel disease, but the principles will be rapidly extended to other important causes of inflammation at other parts of the body. The team is highly complementary, unique, and well-placed to make major advances in the field; ultimately striving to bring benefits to patients, as well as to the wider UK health economy.

Lead Participant

Project Cost

Grant Offer

ORBIT DISCOVERY LTD £299,262 £ 209,483
 

Participant

UNIVERSITY OF OXFORD £200,737 £ 160,590

Publications

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