{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:41:16Z","timestamp":1791499276803,"version":"4.3.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cytomegalovirus (CMV) reactivation is a major cause of mortality following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The application of conventional therapies is limited by hematologic and renal toxicities (ganciclovir and foscarnet) or time-consuming preparation (CMV-specific cytotoxic T lymphocytes [CTLs]). We previously demonstrated the efficacy and safety of CMV-specific T-cell receptor-engineered T (TCR-T) cells for treating CMV reactivation post-haplo-HSCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a phase 2 trial using the previously established highest dose to evaluate efficacy and safety as first-line therapy in a larger cohort. Patients received CMV TCR-T cell infusions (5 \u00d7 10\n                      <jats:sup>5<\/jats:sup>\n                      cells\/kg) upon detection of &amp;gt;1 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      copies\/mL CMV DNA in two consecutive tests or &amp;gt;1 \u00d7 10\n                      <jats:sup>4<\/jats:sup>\n                      copies\/mL once. A second infusion was administered when TCR-T cell expansion remained undetectable within 7 days, and CMV load remained above 1 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      copies\/mL. Salvage therapy was initiated when complete remission (CR) was not achieved after 3 weeks. The primary endpoint was the 4-week CR rate. TCR-T cells were derived from healthy donors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 25 patients enrolled, 13 developed CMV reactivation and received TCR-T cell therapy. Twelve (12\/13, 92.3%, 95% CI: 66.7%\u201398.6%) achieved CR by week 4. Eleven (11\/12, 91.7%, 95% CI: 64.6%\u201398.5%) maintained CR without further antiviral therapy, with median follow-up of 1011 (range: 657\u20131561) days post-infusion. Two cases of grade 1 cytokine release syndrome (CRS) occurred. TCR copy number increased \u226510\n                      <jats:sup>4<\/jats:sup>\n                      -fold within 14 days and remained detectable for 4 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight the long-term efficacy and safety of TCR-T cells as first-line therapy for CMV reactivation post-haplo-HSCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>www.clinicaltrials.gov<\/jats:ext-link>\n                      , identifier NCT05140187.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1820399","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:44:34Z","timestamp":1778737474000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CMV-specific T-cell receptor-engineered T-cell therapy as first-line treatment for CMV reactivation after haploidentical hematopoietic stem cell transplantation: a phase 2 trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingwen","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Senior Department of Hematology, The Fifth Medical 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhua","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Medical Center of Chinese PLA 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