Adoptive Virus-Specific T Cell Therapy for Viral Infections After Allogeneic Hematopoietic Stem Cell Transplantation: Current Strategies and Future Perspectives

Viral infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), particularly in patients with delayed immune reconstitution or prolonged immunosuppression. Although antiviral drugs have substantially reduced the incidence of viral disease, their use is limited by toxicity, resistance, and the inability to restore long-term antiviral immunity. Adoptive transfer of virus-specific T cells represents a targeted immunotherapeutic strategy to re-establish pathogen-specific immune responses while minimizing the risk of graft-versus-host disease (GvHD). This review focuses on the development and clinical application of adoptive virus-specific T cell therapy after allogeneic HSCT, with particular emphasis on cytomegalovirus (CMV). We summarize the evolution of adoptive antiviral T cell therapy, compare current manufacturing and selection strategies, and critically review available clinical evidence regarding efficacy, persistence, safety, and alloreactivity. In addition to CMV-directed products, we discuss approaches targeting Epstein–Barr virus (EBV), adenovirus (AdV), and other clinically relevant pathogens in the context of multipathogen-specific T cell products and third-party donor approaches. We further address current knowledge on immune monitoring, factors influencing antiviral immune reconstitution, as well as practical challenges that still limit broader clinical use. Finally, we discuss emerging strategies to improve product standardization, availability, and integration of adoptive T cell therapy with modern antiviral prophylaxis and graft-engineering approaches.