The study, led by professionals from the Hematology Department of the Hospital Universitario Marqués de Valdecilla (HUMV) and the Advanced Therapies Unit of the Cantabria Blood and Tissue Bank (BSTC), has observed a preliminary reduction in cytomegalovirus (CMV) reactivation from 53% to 36% through the infusion of donor-derived virus-specific lymphocytes.
Researchers from the Hematology Department of HUMV, the Advanced Therapies Unit of BSTC – Fundación Marqués de Valdecilla (FMV) and the SCReN clinical trials platform have published the first results of a clinical trial evaluating a new cell therapy strategy to prevent CMV reactivation in patients undergoing allogeneic bone marrow transplantation.
The study, which also involved patients from the Hematology Department of Hospital Universitario de Salamanca, demonstrates the preliminary feasibility and safety of a strategy based on the selection and administration of CMV-specific lymphocytes obtained from the transplant donor.
One of the main complications that people receiving an allogeneic bone marrow transplant may experience is infection. The treatment and immunosuppression required during the process temporarily reduce the immune system’s ability to defend itself, facilitating the reactivation of certain viruses.
CMV is one of these viruses and is a common and potentially serious infection in this type of patient. Although effective preventive treatments are available in some cases, not all patients can benefit from them, so there remains a need to develop new strategies to reduce the risk of reactivation.
Using the donor’s own cells to strengthen the immune response
The strategy evaluated in this trial involves obtaining lymphocytes from the bone marrow donor and selecting those that show specific activity against CMV.
These cells are processed and selected using an automated system that enables them to be produced rapidly, over approximately one night, and are subsequently administered to the patient at one of the times when they are at greatest risk of developing the infection.
The aim is therefore to provide patients with a specific immune response against the virus and accelerate the recovery of their immune defenses following transplantation.
The study builds on the team’s previous experience in this field. Dr. Óscar M. Pello, from the BSTC Advanced Therapies Unit, has experience in developing this type of virus-specific lymphocyte, while Dr. Arancha Bermúdez, from the HUMV Hematology Department, specializes in infections that may occur following transplantation.
A preliminary reduction in virus reactivation
The published results correspond to an interim analysis of the INMUNOCELL clinical trial. To date, 14 patients have received an infusion of CMV-specific lymphocytes and have completed one year of follow-up.
The data show that virus reactivation during the first 100 days after transplantation occurred in 36% of treated patients, compared with 53% observed in a historical reference cohort at the center.
In addition, all recorded reactivation episodes resolved without the patients developing CMV disease.
The study has also shown a preliminary acceptable safety profile. Three patients experienced mild infusion-related reactions, which resolved without the need for corticosteroid treatment. No increase in acute graft-versus-host disease was observed compared with the historical cohort.
The researchers nevertheless emphasize that these are still preliminary results, obtained in a limited number of patients. The planned patient recruitment must therefore be completed and the final analysis carried out to confirm the potential clinical benefit of this strategy.
Cell therapy beyond cancer
The study is part of the growing development of cell therapies, one of the areas of greatest progress in current medicine, and within which Cantabria has strengthened its position through the Cantabria Advanced Therapies system (TerAVal).
These treatments use living cells as a therapeutic tool to treat or prevent disease. Their application is particularly well known in the field of hematological cancers thanks to the development of CAR-T therapies, but the potential of cell therapy also extends to other areas, such as infections and certain immunological and rheumatological diseases.
The ability demonstrated in this study to rapidly select and produce virus-specific lymphocytes opens up new possibilities for developing cell-based treatments targeted at specific patient needs.
Half a million euros to support the trial
The development of this clinical trial has been made possible thanks to funding obtained through a competitive national call from the Carlos III Health Institute (ISCIII), with a research project funded with €560,000.
The funding has enabled the launch of research that brings together the clinical expertise of the Hematology Department, the BSTC’s cell production and processing capabilities, and the infrastructure required to conduct the clinical trial.
The next steps involve completing the planned patient recruitment and follow-up in order to confirm the results obtained so far.
At the same time, the team continues to advance in the field of cell therapies. It has recently secured new funding of more than €1.34 million to develop a strategy based on another type of cell, iNKT cells, aimed at treating acute myeloid leukemia in older adults. This new project will be led by Dr. Mercedes Colorado from the Hematology Department.
These results further demonstrate the capacity of research and healthcare teams linked to Valdecilla and Cantabria to develop and translate into clinical practice new advanced therapy strategies aimed at addressing patients’ unmet needs.
Photo: Part of the team responsible for the study
