Celebrating Excellence in Blood and Transplant Research

Mara Cenerenti: Uncovering the potential of unexpected killer cells for cancer treatment

White blood cells: the tiny soldiers battling cancer

White blood cells are like tiny soldiers in our body’s powerful defence system, protecting us from potential dangers. One of the most challenging and widespread dangers is cancer, a disease in which cells grow without control and become harmful. Scientists have discovered that our white blood cell soldiers can fight cancer, through a revolutionary treatment called immunotherapy, which was awarded the Nobel Prize in 2018.

What’s new?

Recent research, including our own, has made a surprising discovery. A special type of white blood cell soldier, called CD4 T cells, usually known for supporting other immune cells, can also directly attack and eliminate cancer cells. By using these untapped cells, we could improve current cancer treatments, which have limitations in fighting both solid and blood cancers. However, we still do not fully understand how these special cells develop, what they look like, and what tools they use to eliminate cancer cells.

What will we do?

 To address these knowledge gaps, in this project we will:

• collect and analyse white blood cells from healthy donors.
• examine over 300 aspects of this special type of white blood cell soldier to identify unique markers that distinguish them.
• use advanced tools to study the biological instructions that control their development and ability to eliminate cancer cells.

What is our final goal?

Our goal is to identify unique markers that allow us to isolate these powerful “killer soldier cells”. We also aim to uncover the biological instructions that guide them in eliminating harmful cancer cells. This knowledge could lead to new strategies for harnessing the full power of these special cells in medical treatments, offering new hope for effective cancer elimination.

Akshay Shah: Development of a key performance indicator set for patients needing a red blood cell transfusion around the time of major surgery

Patients who are undergoing major surgery and experience blood loss often require a blood transfusion. However, the way blood transfusions are used varies widely between hospitals. Inconsistent transfusion practices can affect patient safety and treatment outcomes. To tackle this, we wanted to develop a set of key performance indicators (KPIs). KPIs are measures used to monitor the performance of a service against specific goals. They are used by the NHS to track progress and identify areas for improvement (e.g. average waiting times, patient experience).

We followed a 3-step process:

• Step 1: We reviewed existing studies to find potential KPIs relevant to blood transfusion.
• Step 2: We convened a panel of healthcare professionals (doctors, nurses, researchers) and patients with lived experience of either donating blood or receiving a blood transfusion.
• Step 3: The panel assessed the importance and feasibility of all potential KPIs. Importance was judged on whether it would improve patient outcomes and lead to cost-savings, without causing harm. Feasibility was judged on how easy it would be to collect the relevant information from routine health records.

28 potential KPIs were identified, covering various aspects of transfusion care, such as when to give a transfusion and how to keep patients safe during a transfusion. Some KPIs focused on patient outcomes, including hospital length of stay, infection rates, mortality, and hospital readmissions. The panel recommended 9 KPIs to take forward and evaluate in NHS hospitals. 5 KPIs were not needed, and 14 were thought to be difficult to measure from routine health records.

Our results have been published - https://doi.org/10.1016/j.bjao.2024.100372. Our next step is to test these KPIs, particularly the 9 that the panel recommended, using data from a few hospitals. This will help us make sure they are fit for purpose (quality assurance) before rolling them out across the country.

Alicia Galdon: Making Targeted Treatments for Blood Cancers Using the Power of the Immune System

Currently, blood cancers such as leukaemia are treated with bone marrow transplants. These transplants work because a powerful type of immune cell within the transplant, called a ‘T cell’, can recognise and kill cancer cells. This process is known as ‘graft versus-leukaemia’. However, these T cells can also attack and kill healthy cells in organs such as the skin, liver and stomach, which can lead to a range of serious side effects known as ‘graft-versus-host disease’.

Both of these processes happen because T cells recognise tiny fragments of cells called 'antigens' using a sensor called a 'T cell receptor'. The antigens act like flags – they are displayed on the surface of a cell for the T cell to hunt down and find. When a T cell sees an antigen with its T cell receptor, it can trigger the release of toxic molecules that cause the target cell to self-destruct.

Some of these antigens (flags) are only found on the surface of cancer cells. T cells that target these antigens will specifically kill the cancer cell. However, many of the antigens will be found on healthy cells too, and T cells that target these will cause damage to other organs. We believe that if we can find T cells that specifically target cancer cells and ignore healthy cells, we can use them to develop more targeted treatments for blood cancers with fewer side effects.

 To achieve this goal, our research aims to:

1. Discover which antigens are specifically found on the surface of blood cancer cells, and not on cells from other organs.
2. Develop new ways to test how well T cells see these antigens, and if they are successful at killing.
3. Isolate the most effective and cancer-specific T cells to test as a targeted 'off the-shelf' therapy in a clinical trial.

Jaid Debrah: The assessment of blood donation safety in the UK

Background

Following the identification of HIV (Human Immunodeficiency Virus) as the driving force behind the AIDS pandemic in the 1980s, the UK permanently banned gay and bisexual men/Men who have sex with men (GBMSM) from donating blood.

However, social action and research-supported evidence led to changes in UK blood donation policy in 2021. This focuses more on individual donor behaviour rather than sexual orientation, allowing more GBMSM to donate.

The policy says that those who use the medication PrEP (pre-exposure prophylaxis), to avoid getting HIV, aren't allowed to give blood for 3 months. Also, if you have ever had/been treated for syphilis you should not give blood.

In the UK, 93% of PrEP users are GBMSM and syphilis rates are at an all-time high.

Study

We are monitoring blood safety and whether donors are following donation guidelines, by looking at infections and medications in blood donors as markers that you could associate with an unsafe donor.

Results

84 male blood donors that were positive for syphilis in 2023 were looked at and:

• 6 of them also used the PrEP medications in and around the time of donation.
• From 2018 to 2023, this make a total of 20 male donors that were both PrEP and syphilis positive.

What does it mean?

Our findings show consistent evidence of blood donor guidelines not being followed, posing a risk to the UK blood supply.

It will be vital to improve public health education/communication concerning both sexual health and blood donation, particularly in GBMSM communities.

We also look to target younger GBMSM populations who seemed to have the least amount of PrEP use despite having higher risk of sexually transmitted infections.

We do not wish to discourage the use of PrEP for the sake of donating blood, but to both ensure blood safety and better donor education which will result in better health outcomes for all.

Kaitlin Reid: The Viral Content of Historic Blood Products

Background

The Infected Blood Inquiry examined how people in the 1970s to 1990s became infected with viruses via contaminated blood/blood products. Blood products are used to treat diseases such as haemophilia and immune deficiencies and are produced from mixing many blood donations. Past studies focused on the illnesses caused by the blood products and the success of virus inactivation methods at ‘killing’ specific viruses. Currently, inactivation methods are not used by the NHS.

What is the aim of the study?

The aim was to assess the effectiveness of inactivation methods against a wide range of viruses and discuss whether these methods are suitable for future blood safety and which viruses they work against. This study also aims to provide a deeper understanding of the amount and diversity of viruses within blood products from 1974 to 2014.

What did we do?

A capture panel (like a big fishing net for virus DNA) was used to look for over 100 viruses. We used this to see which viruses were present in blood products before and after the introduction of virus inactivation methods in 1985. The results were presented to patient and public members who receive blood/blood products or are blood donors. The group expressed an openness for virus inactivation methods to be used in the future.

What did we find?

After virus inactivation was introduced, contamination of blood products reduced rapidly. The only viruses observed were Parvoviruses and Pegiviruses which are both common infections in the population and are not currently screened for by blood services. After 1996 no contamination of blood products with viruses was reported.

Why is this important?

If inactivation methods are successful at 'killing' most viruses they could be of interest for preventing new viruses from contaminating blood products. Understanding the limitations of inactivation methods and the full range of viruses they work against helps inform whether they are a suitable option for preventing contamination of blood products with future viruses.

Michael Fu: How many people worldwide have been exposed to hepatitis B virus?

Understanding the Global Burden of Hepatitis B

Hepatitis B is a devastating global health threat, with around 250 million people living with an active infection and over 1 million deaths each year. Many people unknowingly come into contact with hepatitis B, yet there has never been a precise estimate of how many people have been exposed. This missing knowledge makes it harder to diagnose, treat, and prevent infections. The World Health Organization (WHO) aims to eliminate hepatitis B by 2030, but without accurate data, millions may remain undiagnosed and at risk.

What is our study about?

Our research will provide the most reliable estimate of how many people worldwide have ever been infected with hepatitis B. We are analysing thousands of studies that test for a key marker of past infection. By combining data from different countries and populations, we will reveal the true scale of how many people hepatitis B has affected and identify the most affected communities.

How are patients involved?

People with lived experience of hepatitis B are at the heart of our research. Five patient contributors from diverse backgrounds have already helped shape our study. Once we have our results, we will hold a focus group to discuss the findings and their impact. Our contributors will also review our final lay summary to ensure it is clear and accessible.

Why does this research matter?

Without a clear understanding of who has been exposed to hepatitis B, we risk missing opportunities to diagnose, treat, and prevent infections. Our research will provide essential data to support WHO's elimination efforts, helping policymakers and healthcare providers target interventions where they are needed most. By improving awareness and encouraging hepatitis B testing, our work will ultimately lead to a future where fewer lives are lost to this preventable disease.

It is important to maintain blood donors’ blood iron store for their health. Haemoglobin is a good indicator of blood iron level. England’s national blood service currently tests every donor’s haemoglobin level before donation. This approach ensures most donors donate safely with enough iron in blood. However, under the current approach, many donors are refused to donate blood after detecting low haemoglobin levels (also known as ‘low haemoglobin deferral’). This leads to a waste of time and money for both donors and donation centres.

Since the current haemoglobin screening approach has low efficiency, we propose a new approach to deal with the problem. In the new approach, we will test most donors’ (77% men and 64% women) haemoglobin levels after donation instead of before. So, they will not be refused to donate during their visits. For those donated with a low haemoglobin level, we will reinvite them after a longer period to allow their iron levels recover. In addition, we will still test first-time donors and those with a low haemoglobin level in the last visit before donation to make sure they have enough blood iron. We expect this approach to be efficient and safe.

Our research team in Cambridge University have developed a computer simulation program to figure out how the new approach would work. We have found that the new strategy could reduce the number of donors who are refused to donate, demonstrating better efficiency. There might be slightly more donations made by donors with a relatively low haemoglobin level, but it would not pose a big threat to donors’ health.

We are working closely with the national blood service to assess the feasibility to implement the new approach in England based on our findings.

Acute myeloid leukaemia (AML) is a blood cancer with a high death risk. Five years after diagnosis, only 41% of younger (60 years) patients survive. The return of AML (relapse) and side effects are common with existing treatments and is why finding better treatments for AML is required.

One approach is to utilise immune cells, such as T cells. These act like soldiers, hunting and destroying virus/bacteria-infected cells or cancer cells. They do this using a sensor called a T cell receptor (TCR), which recognizes warning signs on unhealthy cells (Figure 1). Cells make pieces of protein (peptides) displayed by an HLA protein, which acts as a flagpole, signaling health/disease. We are specifically trying to find TCRs which sense peptides displayed by an HLA type called HLA-E. Unlike other HLA proteins, which vary in different people, everyone has the same HLA-E. Hence, all AML patients could be treated with the same TCR.

We could use a TCR that sees peptide (antigen) found in AML cells exclusively (neoantigen) due to changes in their DNA (mutations). Another option are peptides which are more common in AML than healthy cells (tumour-associated antigens/TAAs). Because AML cells have few neoantigens, we are seeking TCRs that target TAA peptides.

Initially, we found a peptide in a TAA called WT1. We aim to find 2 to 3 backup peptides in case the AML cells stop producing the WT1 peptide. If this happens, T cells are unable to see the AML cells with their TCR. To date, we have found peptides from 7 TAAs which are displayed well by HLA-E. Next, we will test if we can find TCRs for these peptides. If T cells with these TCRs can kill AML cells, this approach could bring hope for AML patients worldwide.

This is a plain language summary of the following published article: Jenkins, R., Rimmer, B., Marson, L., Fisher, A.J., Sharp, L. and Exley, C., 2024. Measuring patient reported experience of solid organ transplantation healthcare: A scoping review of condition-and transplant-specific measures. Transplantation Reviews, p.100872.

What do we already know?

What patients think about their healthcare is an important marker of health service quality. Traditionally, patients’ views have been measured using patient satisfaction questionnaires. There are now more modern types of questionnaires that give more detail about specific aspects of healthcare; what happened, when and how. These questionnaires are called Patient-Reported Experience Measures (PREMs). PREMs give more precise measurements to guide improvements to health services.

What is this research about?

We aimed to identify and describe the existing questionnaires measuring the healthcare experience of people receiving solid organ transplants.

What did we do?

We systematically searched through seven formal online databases of scientific publications. Two researchers screened the all the search results looking for all publicly available questionnaires designed for solid organ transplant recipients. We included PREMs and satisfaction questionnaires if they asked about the processes of healthcare. We did not include questionnaires that asked about patient outcomes, for example symptoms or quality of life.

What did we find?

• We identified only 8 patient experience questionnaires in total, either for kidney or liver transplants. There were no questionnaires for heart, lung, pancreas or intestinal transplantation.
• The questionnaires' content varied. Only 4 surveys asked specifically about transplant-related healthcare, 4 asked about more general kidney or liver healthcare.
• 4 of the questionnaires were designed as satisfaction measures and 4 as modern PREMs.
• Only 6 questionnaires described how they were developed, and only three described how they were tested.

What does this mean?

We found no questionnaires designed as modern PREMs and specific to transplantation that provided enough detail about how they were written and tested. We have shown a need to develop and test new PREMs specific for solid organ transplantation, with clear details of all the steps involved in writing and testing these new PREMs.

• Foram Khatsuria, BTRU in Precision Cellular Therapeutics
• Yaning Wu, BTRU in Donor Health and Behaviour