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However, its long\u2010term efficacy and persistence must be enhanced. T memory stem cells (TSCMs) with superior self\u2010renewal and multilineage differentiation potential may enhance VSTs durability, although their antiviral capacity is underexplored. Cytomegalovirus (CMV)\u2010and Epstein\u2013Barr virus (EBV)\u2010specific T cells are enriched with CD8\u207a TSCM through cytokine and peptide stimulation. Comprehensive preclinical evaluations show that purified TSCM\u2010VSTs exhibit reduced exhaustion, enhanced expansion, and stronger antiviral activity than central or effector memory VSTs (TCM or TEM). Transcriptomic and epigenetic analyses show significant enrichment of the MAPK and Wnt signaling pathways, consistent with stem\u2010like characteristics. In a murine model, CD8\u207a TSCM VSTs provide more effective protection against Raji\u2010pp65 tumors than TCM or TEM VSTs. In a phase I clinical trial, 10 patients with refractory CMV or EBV infections post\u2010transplant who received third\u2010party, off\u2010the\u2010shelf TSCM\u2010enriched VSTs show a 100% overall response rate and 70% complete response, with persistence up to 12 weeks and no severe adverse events. These findings support TSCM\u2010enriched VSTs as a potent, scalable antiviral immunotherapy and highlight TSCM proportion as a critical determinant of VSTs efficacy.<\/jats:p>","DOI":"10.1002\/advs.202510288","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:36:08Z","timestamp":1765186568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Efficacy of Adoptive Transfer of Stem Cell Memory Enriched Virus Specific T Cells against CMV and EBV"],"prefix":"10.1002","volume":"13","author":[{"given":"Xun\u2010Hong","family":"Cao","sequence":"first","affiliation":[{"name":"Peking University People's Hospital, Peking University Institute of Hematology National Clinical Research Center for Hematologic Disease Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies Peking University  Beijing 100044 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