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Current treatments, including antiviral drugs and adoptive cell therapy with CMV\u2010specific cytotoxic T lymphocytes (CTLs), only show limited benefits in patients. T\u2010cell receptor (TCR)\u2010T cell therapy offers a promising option to treat CMV infections. Here, using tetramer\u2010based screening and single\u2010cell TCR cloning technologies, we identified various CMV antigen\u2010specific TCRs from healthy donors, and generated TCR\u2010T cells targeting multiple pp65 epitopes corresponding to three major HLA\u2010A alleles. The TCR\u2010T cells showed efficient cytotoxicity toward epitope\u2010expressing target cells in vitro. After transfer into immune\u2010deficient mice bearing pp65<jats:sup>+<\/jats:sup>HLA<jats:sup>+<\/jats:sup> tumor cells, TCR\u2010T cells induced dramatic tumor regression and exhibited long\u2010term persistence. In a phase I clinical trial (NCT04153279), CMV TCR\u2010T cells were applied to treat patients with CMV reactivation after HSCT. Except one patient who withdrew at early treatment stage, all other six patients were well\u2010tolerated and achieved complete response (CR), no more than grade 2 cytokine release syndrome (CRS) and other adverse events were observed. CMV TCR\u2010T cells persisted up to 3\u00a0months. Among them, two patients have survived for more than 1\u2009year. This study demonstrates the great potential in the treatment and prevention of CMV infection following HSCT or other organ transplantation.<\/jats:p>","DOI":"10.1002\/ajh.26708","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T13:43:30Z","timestamp":1661694210000},"page":"1453-1463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Efficacy of pp65\u2010specific <scp>TCR\u2010T<\/scp> cell therapy in treating cytomegalovirus infection after hematopoietic stem cell transplantation"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4148-4534","authenticated-orcid":false,"given":"Guangna","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences and Institute for Immunology Tsinghua University School of Medicine  Beijing China"},{"name":"School of Biomedical Sciences Hunan University  Changsha 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