GvHD Atlas Project
Research type
Research Study
Full title
Prospective analysis of tissue-derived immune cells in Graft-versus-host disease (GvHD)
IRAS ID
239143
Contact name
Ronjon Chakraverty
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2018/06/08 , UCL Data Protection Registration
Duration of Study in the UK
5 years, 10 months, 1 days
Research summary
PROSPECTIVE ANALYSIS OF TISSUE-DERIVED EFFECTOR T CELLS IN GRAFT-VERSUS-HOST DISEASE (GVHD)
Allogeneic haematopoietic stem cell transplantation (Allo-SCT) is an effective therapy for various malignant and non-malignant diseases. Mortality rates for patients surviving for more than two years however remain twice as high as that of the general population, with the main causes being the relapse of the primary disease and graft-versus-host Disease (GvHD). Donor effector T cells (TE) are required for the development of GvHD. However, current strategies based on the attenuation/depletion of TE lead to a poor reconstitution of the immune system and increased rates of infection, graft failure and relapse.
The standard first line treatment of GvHD is high-dose corticosteroids. Just one third of patients respond fully to treatment, however, with those developing steroid-refractory disease having an even worse prognosis with a 5-30% overall survival. There is an unmet need for new strategies based on prevention and the identification of at-high risk patients.
Work from our UCL pre-clinical programme has demonstrated marked spatial diversity in gene expression profiles of TE in experimental GvHD; this heterogeneity is ‘instructed’ by tissue-autonomous mechanisms, for example in the gut and skin. We reason therefore that selective targeting of those molecular pathways may be useful in preventing or treating GvHD while avoiding global immunosuppression.
The GvHD Atlas Project (GAP) is designed to determine tissue- and blood- immune cell profiles in patients at the onset of GvHD and in a subset of patients who fail to respond to first line treatment.
The study will involve prospective collection of matched blood and tissue samples (skin or gut) from patients with severe acute GVHD for the purpose of isolating individual immune cell populations
The main purposes of the study are to identify tissue-specific immune cell signatures that are linked to the onset of GvHD or the development of treatment resistance.REC name
London - Brent Research Ethics Committee
REC reference
18/LO/1406
Date of REC Opinion
20 Nov 2018
REC opinion
Further Information Favourable Opinion