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This combination cellular therapy consists of allogeneic or autologous virus-specific T-lymphocytes (VSTs) expanded and sensitized ex vivo to recognize specific antigens of both Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). Developed by companies such as **Atara Biotherapeutics** and **AlloVir**, as well as academic institutions like **Baylor College of Medicine** and **Memorial Sloan Kettering Cancer Center**, the therapy is primarily indicated for immunocompromised patients, such as those following hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), who suffer from refractory viral infections or reactivations. The mechanism involves the adoptive transfer of donor-derived T-cells that provide immediate cellular immunity by recognizing viral proteins (e.g., pp65 for CMV and EBNA1 for EBV) presented on Major Histocompatibility Complex (MHC) molecules. This recognition triggers targeted cytotoxic activity, leading to the lysis of infected cells and the prevention of diseases like EBV-positive post-transplant lymphoproliferative disorder (PTLD) and CMV viremia. The EBV-specific component, tabelecleucel, is approved in Europe, whereas CMV-targeted therapies have reached Phase 3 in various multi-virus configurations.
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