Dr Diana Hernandez Head of Translational Immunotherapy in the Anthony Nolan Research Institute

New research from Anthony Nolan provides clues to improving the success of cord blood transplants

April 10, 2024

Cord blood transplants are a potentially life-saving stem cell transplant option for many people who can’t find an ideal match from an unrelated adult donor or a family member.

Our cord blood donors are mothers who offer to donate their umbilical cord blood – a leftover product from birth that usually gets thrown away – which is carefully stored in our cord blood bank where it could provide a life-saving stem cell transplant for a patient with blood cancer or a blood disorder.

Cord blood transplants involve several differences over stem cell transplants from adult donors. Most importantly, the donor does not need to be as precisely matched to the patient’s tissue type, and there is a lower risk of potentially life-threatening side effects. However, cord blood units typically contain smaller numbers of cells than other sources of stem cell donation, which can sometimes limit their use.

Newly published research from Anthony Nolan has shown that particular genetic characteristics of the cord blood donor could help us select even better cord blood units for transplant. This could improve the way doctors make decisions about which cord blood units might be most suitable for their patients.

We’re really excited to release this new research, which shows the potential of targeted genetic screening of cord blood units in helping to select the best possible transplant donor for every patient. For many, a stem cell transplant is a last hope, and research like this means we can give patients a better chance of a positive outcome.

Dr Diana Hernandez, Head of Translational Immunotherapy at Anthony Nolan.

The research in-depth

When a patient’s doctor is searching for an ideal cord blood unit to use for their transplant, they consider many factors that could make one particular cord blood unit better than others. The doctor will always consider the genetic similarity of the cord blood unit to the patient, in terms of the patient’s ‘tissue type.’ Cord blood units that share the same tissue type as the patient will tend to be a better choice for the patient.

However, the genes that make a person’s tissue type aren’t the whole story when it comes to a transplant. Many other genes are also involved in how blood stem cells behave after they’ve been transplanted – including how well the transplanted cells will move, grow, and fight cancer.

The research team, led by Dr Diana Hernandez and Dr Steven Cox of the Immunotherapy Group at the Anthony Nolan Research Institute, have studied two genes that they suspected to be involved in the behaviour of important white blood cells called natural killer cells.

Natural killer cells (also called NK cells) are a crucial part of our immune system, helping to fight infections quickly and relatively independently. They’re particularly important in stem cell transplants from cord blood, as they are one of the first types of blood cell to grow from the transplanted stem cells. NK cells can help to fight any remaining cancer in the patient, fight off potential infections while the patient is in a vulnerable state, and reduce some of the unpleasant side effects of a stem cell transplant.

The team investigated two genes – NKG2D and MICA – that are involved in how NK cells work. A significant number of us carry variants of these genes that can make NK cells more potent – that is, more capable of fighting cancer and minimising harmful side effects. The Anthony Nolan researchers expected that cord blood units with more potent NK cells might be a better choice for transplant.

Unexpectedly, Diana and Steve’s team found that it really all depends on whether the cord blood unit is being used for a transplant in an adult patient, or in a paediatric patient.

In adult patients, the cord blood units with more potent NK cells turned out to be worse at establishing themselves after the transplant (a process called engraftment). In paediatric patients, this was reversed – cord blood units with more potent NK cells were actually better at engraftment!

Engraftment is really important in any stem cell transplant, because the quicker transplanted stem cells get themselves set up in the patient’s bone marrow and start making healthy blood cells (including NK cells), the faster the patient will be protected from infections and will be able to start fighting any remaining cancer in their body.

The difference between adult and paediatric patients could be due to a number of reasons, since adult transplants work a bit differently to paediatric transplants. Adults are more likely to get a gentler conditioning treatment (the treatment that prepares them for transplant), a relatively smaller dose of cells compared to the size of their body, and less choice of cord blood units with a matching tissue type – all of these things could impact the way the NK cells behave after transplant.

Overall though, these findings mean that if we know which variants of these two ‘NK potency’ genes are present in a cord blood unit, it could give doctors an indication about how quickly the cord blood transplant might engraft in their patient, depending on whether they have an adult or paediatric patient. This could help doctors select more suitable cord blood units for their specific patient.

Our results show that screening cord blood units for these two genes involved in NK cell function could help doctors select cord blood units that could lead to earlier stem cell engraftment, potentially reducing the risks of graft failure, infection, or relapse. This could make a huge different to patients by increasing their chance of having a good outcome from the transplant and potentially a better quality of life afterwards.

Crucially, this discovery also highlights to doctors that the choice of a cord blood unit may depend on the patient’s age, conditioning, and other factors. This just emphasises the importance of increasing our understanding of these genetic factors that affect the suitability of cord blood units for specific patients.

Dr Steven Cox, lead researcher, Anthony Nolan’s Immunotherapy Group.

These results not only show the potential of more in-depth genetic screening of cord blood units for transplant, but also provides researchers with more clues about the behaviours of the crucial NK cells in a cord blood transplant. Knowing more about the genetics of how NK cells work could help scientists develop exciting new cell therapies, such as those being developed by Diana’s team:

We are currently working on several projects specific to NK cells and their potential use in cell therapies that could help support, or even one day replace, typical stem cell transplants for patients with blood cancers and blood disorders.

Dr Diana Hernandez, Head of Translational Immunotherapy, Anthony Nolan

You can read the full study in the European Journal of Haematology here.

Find out more about Anthony Nolan's Immunotherapy research group here.