For patients undergoing a life-saving organ transplant, the road to recovery is often a delicate balancing act. While the new organ offers a second chance, the drugs needed to prevent the body from rejecting it also weaken the immune system, leaving patients vulnerable to dangerous viral infections like Cytomegalovirus (CMV).
In our latest CTGCT Science Talks, PhD researcher Claudia Beltran Mestres from the Berlin Center for Advanced Therapies (Charité – Universitätsmedizin Berlin) shared her work on how automation can help us manufacture “living medicines” to protect these vulnerable patients.
The Challenge: Fighting Viruses When Your Guard is Down and how to Automate It
After a transplant, viruses that a healthy body would easily manage, such as CMV, influenza, or adenovirus, can become life-threatening. While antiviral drugs exist, they often come with harsh side effects.
The alternative? Virus-specific T-cell therapy. This involves taking a patient’s blood, isolating their natural virus-fighting T-cells, and “training” them to multiply in a lab before re-infusing them into the patient. It’s a way of giving the body back its specialized defense force.
Traditionally, scientists grow these cells in standard lab equipment called 24-well plates. However, this is a highly manual, “hands-on” process that requires researchers to change the liquid “food” (media) for the cells every two to three days. Claudia’s research focuses on moving this process into automated, GMP-compliant bioreactors called the G-Rex system.
The G-Rex system significantly improves the production of T-cells compared to manual plates by enhancing efficiency, scale, and safety. Its design allows cells to remain healthy for seven to ten days without a single media change, while also producing a much higher total “yield” or number of T-cells. Furthermore, because these bioreactors operate as a “closed system,” they minimize the risk of contamination, ensuring a safer and more reliable process that is ideal for clinical applications.
Better, Stronger T-Cells and Why This Matters
The research demonstrates that automation doesn’t just increase the quantity of T-cells, it significantly enhances their biological “fitness.” By monitoring specific markers, Claudia found that cells from the automated bioreactor showed lower levels of exhaustion indicators like the PD-1 protein, which often acts as a biological brake on immune activity. This means the T-cells stay in a more “rested” and alert state, ready to respond to threats. Crucially, this improved state does not sacrifice their primary mission, as these cells were proven to be just as effective at identifying and killing viral targets as those grown through traditional, manual methods.
Supporting this superior performance is a more efficient metabolic “engine,” which was identified through the study of metabolomics. By analyzing the chemical footprints within the cells, Claudia found that the bioreactor environment optimizes the TCA or Krebs cycle, the central series of chemical reactions used to generate cellular energy. This allows the T-cells to manage their energy resources more effectively, providing them with the stamina and fuel required to survive and fight infections once they are infused into the patient’s body.
The goal of the TreaT project is to make these advanced therapies faster, cheaper, and more consistent. By automating the manufacturing process, researchers will be able to move these life-saving treatments from specialized labs into hospitals more efficiently, helping more transplant patients regain their health without relying solely on heavy medication.
Finally, we would like to express our gratitude to Claudia Beltran Mestres for her insightful presentation and to Dr. Leila Amini for her invaluable collaboration with this research and the CTGCT project. Claudia is currently a third-year PhD student in Dr. Leila Amini’s research group at the BeCAT. With a strong foundation in biomedical sciences from the University of Girona and advanced immunology training from the University of Barcelona, Claudia is dedicated to bridging the gap between laboratory research and clinical treatment.