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Trivirus-specific cytotoxic T-lymphocytes are ex vivo expanded donor-derived CD8+ T-cell lines engineered to be simultaneously specific for three viruses—typically Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus (AdV)—to prevent or treat opportunistic viral infections after allogeneic hematopoietic stem cell transplantation. These lines are generated by stimulating donor monocytes and EBV-transformed lymphoblastoid cell lines (EBV-LCL) with a chimeric adenoviral vector (to provide adenoviral antigens) and by expressing CMV pp65 to induce CMV-specific reactivity, while EBV-LCL provide EBV antigens, yielding polyclonal CTLs that recognize all three viruses. In early clinical use, low-dose infusions expanded in vivo and appeared to protect against all three target viruses in transplant recipients.[3] As CTLs, their cytotoxic mechanism involves perforin/granzyme-mediated apoptosis and Fas–FasL interactions upon antigen recognition via MHC class I on infected cells.[2]
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