Project Details
Projekt
In depth characterization of naturally occurring and adoptively transferred HAdV-specific T-cells, their ligands and receptors: perspectives for optimizing protective T-cell immunity against HAdV in transplant recipients
Subject Area
Virology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
Human adenovirus (HAdV) infections remain an important cause of severe illness and death in immunosuppressed patients. To recognize patients at risk early and to further improve immunotherapies using HAdV-specific T cells, which are already used in treatment-resistant patients, it is essential to closely monitor and better understand HAdV-specific T-cell immune responses. However, it is still unclear whether T-cell immunity is specific for individual HAdV types. Most of the known viral targets for T cells originate from HAdV-C5, while the broader range of epitopes from other medically relevant subtypes is still poorly understood. In addition, no comprehensive single-cell analysis has yet integrated both the functional and T-cell receptor (TCR) level properties of effective HAdV-specific T cells (HAdV-VST). This project builds on our extensive experience in studying T-cell immunity in immunosuppressed patients and in developing adoptive T-cell transfer (ACT) therapeutics. By combining advanced functional assays, single-cell analyses, innovative human leukocyte antigen (HLA) expression systems, and careful patient stratification, we aim to gain decisive insights into the natural dynamics of HAdV-specific T-cell responses. We aim to understand the mechanisms behind weak immune control and the biologically active T-cell subsets within ACT products. The main goals are: (i) to identify new T-cell epitopes from the most clinically relevant HAdV types and characterize the corresponding T-cell responses in detail, (ii) to measure and functionally evaluate protective HAdV-specific T-cell responses in children after hematopoietic stem cell transplantation (HSCT), and (iii) to perform a high-resolution characterization of HAdV-specific T cells at the TCR and transcriptome level in both patient samples and T-cell products. Overall, we expect to refine risk assessment for severe adenovirus infections, clarify the degree of type-specificity in HAdV immunity, and use these insights to improve the design and clinical efficacy of HAdV-targeted T-cell therapies.
DFG Programme
Research Units
