Group leader
Dr Diana Hernandez is a stem cell biologist with more than 30 years’ experience in medical research and 20 years in the cell therapy field both in academia and industry. She holds a BSc in Genetics from the University of Newcastle, and a PhD in Cancer Genetics from the University of Birmingham.
After several years in basic academic research at Imperial College and University College London, she led several collaborative projects between academia and biotech, first from the academic side and then from the commercial side; all in the area of cell therapy. She worked for six years in a biotech company specialising in stem cell technologies and cell therapy products, where she led the development of an expanded haematopoietic stem cell product derived from cord blood.
She currently leads the Immunotherapy research group at the Anthony Nolan Research Institute. She is also an honorary Senior Lecturer at the UCL Cancer Institute and the vice-chair of the Cell and Gene Therapy Advisory Committee of the Bio Industries Association (BIA).
What is immunotherapy?
Immunotherapy is a type of treatment which harnesses the power of our immune system to tackle disease – cancer in particular.
It takes advantage of the fact that our immune systems are continuously surveying our bodies, finding and identifying abnormal cells (both cancerous and infected), and destroying them.
We can use this functional feature in two main ways. We can deploy small molecules and antibodies as medicines to alter the behaviour of the immune cells of the patient – for example, using checkpoint inhibitors (molecules that re-activate immune cells so they can kill tumour cells). Alternatively, we can ‘supplement’ the immune system of the patient with cells which have been expanded in the laboratory, and sometimes genetically modified to make them more effective at killing target tumour cells, for example CAR-T and CAR-NK cells.
The aims of the Immunotherapy Group
The Immunotherapy Group, in collaboration with the Immunogenetics group and with the support of the Cell Therapy Centre in Nottingham, focuses on two key areas of research with the aim of improving the outcomes of haematopoietic stem cell transplantation:
- Graft content: we know that alongside having a good HLA match, the different cell types and other factors present in the graft each patient receives can influence the transplant’s outcome. We are studying the different cells that make up the graft, as well as the genes they express, and linking it to transplant outcomes. This will give us a better understanding of what makes an optimal graft for a given patient, when we select future donors.
- New cell therapies for post-transplant complications: cellular therapies such as CAR-T cells are currently only available for certain indications, but they have shown already remarkable results and great potential for the future. We are exploring ways of developing novel cell therapies from umbilical cord cells, to prevent or treat the most common causes of mortality after transplant: relapse and graft vs host disease (GvHD).
What impact will this have for stem cell transplant patients?
A stem cell transplant is a curative therapy for many blood cancer patients. However, around 50% of patients that receive a transplant do not survive beyond five years, often due to relapse. Many patients also have to cope with difficult complications of treatment including GvHD and severe infections.
By improving our understanding of what constitutes a good graft at the cellular and sub-cellular level and developing exciting new cell therapies that are more accessible to patients, we hope to improve the quality of life for all transplant patients in the future.
Team members
- Dr Steven Cox, Senior Postdoctoral Research Scientist
- Dr Catarina Martins Freire, Postdoctoral Research Scientist
- Ms Anna Etzenberger, PhD candidate
- Mr Edward Vernon-Purves, Research Assistant
Current research projects
Stem cell donor immune profiling
When a patient receives a haematopoietic cell transplant (HCT), all the cells collected from the donor are infused. The graft contains not only the stem cells, which will go on to reconstitute the immune system of the patient, but also other cells which help the patient fight infections and even fight cancer. However, these ‘other’ cells are not always well defined and are likely to be different between donors. We also don’t understand if these differences in the composition of the graft impact the transplant outcome or the complications a patient may experience post-transplant. Therefore, the aim of this project is to try and dissect these differences by characterising the immune profile of donors and investigate any correlations with patients’ outcomes.
For this project we so far have analysed immune gene expression in a panel of 100 donors using Nanostrings technology. We are currently analysing the data to narrow down possible biomarkers which could be used in the future to predict or even select the best donors for each patient based not only on their HLA compatibility, but also their immune profile.
Cord blood immune profiling
Similarly to the work we are undertaking in adult donors, we are also trying to understand how the composition of cord blood units impacts engraftment and clinical efficacy.
This project is a collaboration between Anthony Nolan, The University of Edinburgh, Banc di Sang et Texis, Eurocord, Aachen University, Teesside University and Gothenburg University, funded by the MRC.
Using NK cells to treat relapse
Although transplant can be a curative therapy for blood cancer, in a certain proportion of patients, the cancer comes back. This is referred to as relapse, and it can be difficult to treat with standard chemotherapy. This is why we are investigating the use of a cell immunotherapy to treat relapse based on umbilical cord-derived natural killer cells (NK cells). NK cells are part of the innate immune system (our first line of defence against infection) and their function is to monitor, detect and eliminate cells which are abnormal through infection or cancer to keep the organism healthy. In cancer patients these cells are no longer able to perform the function correctly, but we can reinstate them by infusing third party (from a donor) NK cells which have been grown in the lab.
NK cells can be isolated from the peripheral blood of adults or from umbilical cord blood (UCB) which is collected from the placenta following birth. These cells can be expanded in the laboratory and have shown to be safe and efficacious when infused into patients, even when the donor is not HLA matched to the patient.
We have been able to show that inherent variation between donor cells, which had previously been thought to hamper efforts to use UCB, can be greatly diminished if certain donor characteristics and processing parameters are adhered to. By optimising the selection and isolation of the starting material, we now have a starting platform for the development of a NK cell therapy. Next, we are working on two further developments in parallel. One is the precise genetic editing of the NK cells to increase their activity using CRISPR Cas technology, and the second is the development of enhanced media and culture conditions to maximise the ex vivo expansion of the cells to make them in sufficient quantities to dose multiple patients.
Key publications
Umbilical cord blood natural killer cells for adoptive immunotherapy: identifying optimal starting material and processing parameters. Kennedy, M., Patterson, W., Cox, S., Wynn, L., Stock da Cuhna, C., O’Dwyer, M., Danby, R., Hernandez, D. Frontiers in Immunology (2026) 16:1734453. doi: 10.3389/fimmu.2025.1734453
Highly proliferative and freeze-thaw resilient CD56neg early natural killer cells in umbilical cord blood: an overlooked starting population for adoptive cell therapy. Kennedy, M., Patterson, W., Cox, S., Danby, R., Hernandez, D. (2025) Cytotherapy, 27S181
Early isolation and cryopreservation of nk cells from fresh cord blood, enhances their subsequent performance. Patterson, W., Cox, S., Danby, R., Hernandez, D. (2024). Cytotherapy, 26S176
Previous work from ANRI in NK biology
Umbilical Cord Blood Natural Killer Cells, Their Characteristics, and Potential Clinical Applications.
Sarvaria, A., Jawdat, D., Madrigal, J. A., & Saudemont, A.
Frontiers In Immunology (2017), 8, 329.
Cryopreservation has no effect on function of natural killer cells differentiated in vitro from umbilical cord blood CD34(+) cells.
Domogala, A., Madrigal, J. A., & Saudemont, A.
Cytotherapy, (2016) 18(6), 754–759.
Natural Killer Cell Immunotherapy: From Bench to Bedside.
Domogala, A., Madrigal, J. A., & Saudemont, A.
Frontiers In Immunology (2015) 6, 264
Differential activation of cord blood and peripheral blood natural killer cells by cytokines.
Alnabhan, R., Madrigal, A., & Saudemont, A.
Cytotherapy (2015), 17(1), 73–85.
The unique profile of cord blood natural killer cells balances incomplete maturation and effective killing function upon activation.
Luevano, M., Daryouzeh, M., Alnabhan, R., Querol, S., Khakoo, S., Madrigal, A., & Saudemont, A.
Human Immunology (2012), 73(3), 248–257.
Transcription factors involved in the regulation of natural killer cell development and function: an update.
Luevano, M., Madrigal, A., & Saudemont, A.
Frontiers In Immunology (2012) 3, 319.
Using cord blood derived mesenchymal stromal cells (MSCs) to treat GvHD
MSCs are known to be immunomodulatory and can also promote tissue repair. These properties, plus the fact that the immune system does not react to them, make them ideal candidates for cell therapy, especially for conditions such as graft vs host disease (GvHD). They exert theses effects through a wide range of signalling molecules they secrete including IDO, several interleukins, PD-Ls and HLA-G5.
MSC-based therapies to treat immune diseases have performed inconsistently in clinical trials, potentially due to variation on how these cells are defined, collected and grown for clinical use as well as the intrinsic biological differences between donors. In addition to the challenges associated with the biological variation of MSCs, the ambiguity regarding their mechanism of action further complicates their clinical translation.
This project aims to address the issues associated with the functional variation between umbilical cord MSCs derived from different donors which results in inconsistent therapeutic effects and prevents the development of standardised MSC products. By dissecting the interactions between umbilical cord MSCs and immune cells, we aim to reveal mechanisms and targets which can be manipulated in order to reduce functional variation between MSCs from different donors. Additionally, differences in the expression or secretion of immunomodulatory molecules between MSCs derived from different donors will be assessed in order to elucidate signatures that can determine/predict the potency (how well they are able to modulate the immune system) of donors.
Publications
131 - Mesenchymal Stem/Stromal Cells: Characterisation of HLA-G isoform expression in umbilical cord – derived mesenchymal stromal cells and their potential effect on immunomodulation. Strange, K., Cox, S., Patterson, W., Lucas, J., Turner, T., Danby, R., Hernandez, D. (2022) Cytotherapy, 24S56
Mesenchymal Stem/Stromal Cells: Inter–donor differences in the secretome of umbilical cord–derived mesenchymal stromal cells correlated with differences in their in vitro immunosuppressive function. Strange, K., Fernando, R., Danby, R., Hernandez, D. (2023) Cytotherapy, 25S93.
Mesenchymal Stem/Stromal Cells: Impact of HLA–G isoform expression and post– translational modifications on the immunosuppressive potency of umbilical cord–derived mesenchymal stromal cells. Strange, K., Cox, S., Patterson, W., Lucas, J., Turner, T., Danby, R., Hernandez, D. (2023) Cytotherapy, 25S9