2007 - The molecular basis of mucosal T cell homing to the liver in primary sclerosing cholangitis

Professor David Adams
Based: University of Birmingham
Donor: Violet Richards Charitable Trust
Amount: £97,483
Start date: October 2007
Completed: February 2010

Title of study: The molecular basis of mucosal T cell homing to the liver in primary sclerosing cholangitis.

To download the lay summary of this research please click on the PDF below:
Lay Review Adams.pdf

Lay summary of findings
Much of the initial work done on this grant led to basic science advances to characterise the conditions that leads to T-cell and regulatory T-cell generation in patients with primary sclerosing cholangitis. We established that in order to generate regulatory T-cells one requires stimulation of the T-cell receptor as well as the presence of retinoic acid to generate regulatory T-cells that are able to traffic preferentially to the liver and the gut (this body of work is extensively described in our interim report which is included). This work has since been published in Gastroenterology. In order to exploit this data therapeutically, we have spent much of this last year performing preclinical development of large scale harvesting and generation of regulatory T-cells to be used as a therapy in patients with PSC (primary sclerosing cholangitis) and IBD (irritable bowel disease).

Impact of the research
The work has now led to ethical committee approval to harvest leukapheresis generated T-cells from patients with PSC and to isolate from these products regulatory T-cells in a manner which is GMP compliant. We have also gained R&D approval from the University Hospitals Birmingham NHS Trust to proceed with this line of investigation. The study has also been adopted within the West Midlands Clinical Research Network. Copies of these approvals are attached to this document. We hope to recruit our first patient within the next six weeks to generate therapeutic regulatory T-cells to treat these patients.

This grant has provided us with an opportunity to not only define the basic science that underpins this important line of investigation but also have facilitated the pre-clinical development of this knowledge to a potential clinical therapy.

Download the full Final Report

Professor Adams’ research has been published in the following scientific journals:

Gastroenterology

The paper can be read as part of Professor Adams’ Final Report.