VST manufacturing strategies. Donor blood is drawn and PBMCs are then manipulated using different approaches for the manufacture of VSTs for clinical use. (A) Direct selection utilizes either: (1) multimers specific for a virus-derived peptide in the setting of a class-I HLA molecule, or (2) column selection where T cells are stimulated with viral antigen followed by selection of IFN-γ or CD154–expressing T cells using antibody coated immunomagnetic beads. (B) Ex vivo T-cell expansion requires the in vitro stimulation and expansion of T cells using APCs pulsed, infected, or transfected with viral peptide(s)/protein(s), viral lysate, or viral vectors/plasmids, respectively. (C) Genetic modification requires the gene transfer of high affinity VST receptors or chimeric-antigen receptors to redirect specificity of T cells to viral targets. CAR, chimeric antigen receptor.