Virus-Specific T-Cell Therapy for the Management of Viral Infections in the Immunocompromised

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) – a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the clinical potential of adoptively transferred virus-specific T cells (VSTs) to prevent/treat virus-associated complications after allo-HCT or solid organ transplantation (SOT) and this review will provide an overview of these endeavors. Summary: This review will focus on the progress that has been made over the past 30 years in the field of nonengineered VST manufacturing technologies and will summarize the clinical experience with VSTs, primarily in the posttransplant setting. Key Messages: Over the last 3 decades, adoptively transferred VSTs – both HCT donor and third party-derived – have been tested in numerous single and multicenter clinical trials and have unequivocally proven to be safe and associated with clinical activity.