Stem cell transplant research breakthrough gives hope to those with blood cancer

Researchers at the University of Birmingham affiliated to the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) have identified a key target, CD70, to reduce the likelihood of ‘graft-versus-host disease’ (GVHD) which people with blood cancer can develop after receiving a life-saving stem cell transplant. The research, published in Blood Advances and funded by Blood Cancer UK, suggests that graft-versus-host-disease could one day be detected and treated.

Blood cancer is the UK’s fifth most common cancer, and with it also the UK’s third biggest killer, new and kinder treatment approaches are desperately needed. Around 1000 people a year receive a type of stem cell transplant called an allogeneic hematopoietic stem cell transplant. This can be a life-saving treatment which uses healthy cells from a donor to replace a patient’s damaged blood and immune cells.

However, this procedure has a risky side effect called graft-versus-host disease (GVHD), which can occur in between 30 to 70% of cases. In GVHD, the donor’s immune cells (the “graft”) mistakenly attack the patient’s body (the “host”), which can lead to serious and even life-threatening complications. Finding ways to better understand and manage GVHD is crucial for the safety and success of these transplants.

In this study, Professor Paul Moss and his team at the University of Birmingham, led by Dr Kriti Verma, took a closer look at a specific type of immune cell that could help doctors develop better treatments for GVHD. They focussed on a molecule called CD70, which appears on the surface of immune cells called T-cells soon after a stem cell transplant.

“Our lab tests showed that blocking the interaction between CD70 and its partner molecule, CD27, reduced the aggressive behaviour of these T-cells. This suggests that interrupting this CD70-CD27 signal could be a new way to treat or even prevent GVHD by calming down the overactive immune response.”

Dr Kriti Verma, University of Birmingham

The team found that CD70 was present on T-cells within the first two weeks after transplant, during a crucial period for GVHD development. They were also highly predictive of the disease developing. The CD70-positive T cells were also more active and showed a unique genetic activity that made them ready to use energy and multiply quickly, two factors associated with the inflammatory responses that drive GVHD.

Dr Verma, Postdoctoral Research Fellow at the University of Birmingham’s Department of Immunology and Immunotherapy and researcher within the Cancer Inflammation theme at the NIHR Birmingham Biomedical Research Centre, said:
“T-cells are key players in the body’s immune response, and CD70 shows up on them when they’re highly active—especially when they’re responding aggressively to what they see as foreign, such as the patient’s own cells in graft-versus-host disease (GVHD).”

“Interestingly, in those with acute GVHD, the number of CD70-positive T-cells spiked, and these cells were found in tissues affected by GVHD. Our lab tests showed that blocking the interaction between CD70 and its partner molecule, CD27, reduced the aggressive behaviour of these T-cells. This suggests that interrupting this CD70-CD27 signal could be a new way to treat or even prevent GVHD by calming down the overactive immune response.”

The research team now hopes to be able to move into clinical trials to help develop an early diagnostic test for GVHD, which currently doesn’t exist. They also want to develop treatments that target CD70 to better control GVHD without suppressing the whole immune system.

Speaking about the research and hopes for the future, Dr Verma, said:
“The impact of this research is significant because it points to CD70 and its partner CD27 as a way of identifying the specific T-cells driving graft versus host disease (GVHD). Because CD27 is cleaved and found in the blood we think we could measure it and use it as early diagnostic marker for GVHD in a blood test. We’re very well placed at the University of Birmingham to try and take this work forward and with our insight we hope to develop better diagnostics and treatments for GVHD without suppressing the whole immune system. For people with blood cancer undergoing stem cell transplants, this could mean a safer road to recovery and a better chance at a healthy life after treatment.”

A hidden illness

Jane Leahy, aged 51 from Wimbledon, lives with GVHD after receiving a stem cell transplant during treatment for a type of blood cancer called acute myeloid leukaemia. Speaking about the condition she said:
“It’s really hard to live with this hidden illness, often no one knows what graft-versus-host disease even is; I’ve spoken to doctors who didn’t. The disease always impacts my life, I can’t even go away for a weekend without thinking about my treatment regime, it’s a constant thing that you have to think about. Physically, I do all I can, but my lung function has declined significantly. I move slower than I’d like, and even going upstairs leaves me out of breath— it’s a constant weight on my shoulders.”

“No one knows how my graft-versus-host disease will develop, but I’ve been told it’s never going to get better. Although it won’t help me, I’m so pleased that Blood Cancer UK is funding research to shed light on this debilitating condition to help others. If this research plays a part in getting closer to people receiving a stem cell transplant being able to walk away without any long-term health impact, that’s an amazing, exciting prospect.”

Dr Richard Francis, Deputy Director of Research at Blood Cancer UK, said: “Our UK-wide blood cancer action plan highlighted the life-limiting side effects of current treatments and that survival rates for blood cancer in the UK lag behind nations of similar wealth and health. These lab-based findings mark an important first step in developing kinder treatments for people with blood cancer. This progress wouldn’t be possible without our supporters’ generosity or the researchers’ expertise. For people like Jane, we are committed to working towards a future where no one dies from blood cancer or its treatments.”