Completed Cancer Heart, Stroke & Blood

Generation of suppressive donor T cells to specifically control alloresponses after allogeneic stem cell transplantation

Funder MRC (part of UKRI)
Recipient organisation Queen Mary University of London
Funding £1.5M
Period Jan 2011 — May 2015

In plain English

AI plain-English summary

A donor’s immune cells, trained in the lab before transplant, can be turned into suppressors that stop them from attacking the patient’s healthy tissues. This matters because graft-versus-host disease (GVHD) remains the biggest barrier to successful stem cell transplants for blood cancers like leukaemia. Current prevention drugs wipe out all immune cells, leaving patients vulnerable to infections and cancer relapse. The researchers have already found a lab method to produce human donor cells that specifically suppress GVHD responses. This project aims to refine that technique so the cells can be reliably manufactured for clinical use. If the approach works, it could make stem cell transplantation safer and more effective—reducing the need for broad immune suppression and allowing the patient’s own immune system to recover normally. That would mean fewer infections, less relapse, and a better chance of long-term cure for people with otherwise incurable blood cancers. The research is at a pre-clinical, laboratory stage, but it directly targets a practical bottleneck in transplant medicine.

View original technical description
Allogeneic stem cell transplantation consists of the transfer of blood stem cells (or bone marrow) from a healthy donor to a patient. This procedure can cure patients with many diseases that would be otherwise incurable, including those with cancers of the blood such as leukaemia. However, a major problem that limits the success of allogeneic stem cell transplantation is graft-versus-host disease, which is the destruction of healthy patient tissues by donor immune cells contained within the transplant. Current techniques to prevent graft-versus-host disease are unsatisfactory as they suppress the recovery of all immune cells, resulting in increased infection and cancer relapse after transplant. We have recently identified a way of manipulating human donor cells before allogeneic transplantation that leads to the production of immune cells which can suppress graft-versus-host disease responses. The aim of this project is to develop ways in the laboratory to improve this technique to provide donor immune cells which could be used to prevent graft-versus-host disease without affecting the healthy recovery of the immune system after allogeneic transplantation. We hope that this might lead to a better way to prevent graft-versus-host disease after allogeneic transplantation, making this a safer and more effective treatment.

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Researchers

Jeffrey Davies (Principal Investigator)

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Original classification

Fellowship

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