[Third-party virus-specific T-cell therapy for treatment-resistant viral infections after hematopoietic cell transplantation]

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe disorders, including refractory hematologic malignancies and inborn errors of immunity. The increasing use of HLA-haploidentical transplantation and intensive immunosuppressive strategies has resulted in a growing population of patients at high risk for post-transplant viral infections. Viral infections after HCT are often refractory to currently available antiviral agents and remain a major cause of transplant-related morbidity and mortality. Effective viral control requires the reconstitution of virus-specific immunity; however, donor-derived antiviral immune responses often take considerable time to develop after transplantation. Against this background, virus-specific T-cell (VST) therapy has emerged as a promising immunotherapeutic approach. Recent advances have led to the development of third-party (TP), off-the-shelf VST products and multi-virus-specific T-cell (MVST) products capable of targeting multiple viruses simultaneously. Cryopreserved VST products enable rapid therapeutic intervention for patients with refractory viral infections. Furthermore, the approval of tabelecleucel for Epstein-Barr virus-associated post-transplant lymphoproliferative disease in Europe marks an important milestone in the clinical translation of VST therapy. This review summarizes the history, manufacturing strategies, clinical development, and key clinical trial results of VST therapy, with a particular focus on TP-VST and TP-MVST platforms and their development in Japan.