{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:27:13Z","timestamp":1783078033932,"version":"3.54.6"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023479","name":"CRIS Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Respiratory viral infections remain a major global health challenge, particularly in immunocompromised populations. Although adoptive cell therapies using virus-experienced memory T lymphocytes have demonstrated safety and effectiveness when administered intravenously, the safety profile and feasibility of intranasal delivery of immune effector cells in humans was not previously assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      vRELEASE I (NCT06699758) represents a phase I, single-center, open-label, dose-escalation study designed to evaluate the safety profile and feasibility of intranasal administration of off-the-shelf, allogeneic CD45RO\n                      <jats:sup>+<\/jats:sup>\n                      \/RA\n                      <jats:sup>\u2212<\/jats:sup>\n                      memory T lymphocytes derived from a third-party male donor in healthy female adult volunteers. The study employed a conventional 3+3 dose-escalation design, evaluating three dose levels (1 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      , 5 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      , and 10 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      cells per dose). Each participant received three intranasal administrations at 2-h intervals. Safety assessments included monitoring for adverse events and dose-limiting toxicities (DTLs). The local persistence of donor-derived cells in the nasal mucosa was evaluated using fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization (FISH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intranasal administration was completed as planned in all nine treated participants. No treatment-emergent adverse events were observed in any cohort during the seven-day safety follow-up period. The highest planned dose, 10 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      cells per administration, was delivered to three participants without DLTs during short-term follow-up. Donor-derived male cells were not detected above the assay detection threshold in evaluable nasal mucosa samples by Y-chromosome FISH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this first-in-human, single-center phase I dose-escalation study, intranasal administration of third-party, ready-to-use, allogeneic CD45RO\n                      <jats:sup>+<\/jats:sup>\n                      \/RA\n                      <jats:sup>\u2212<\/jats:sup>\n                      memory T lymphocytes was well tolerated. No treatment-emergent adverse events or DTLs occurred during the seven-day follow-up of nine healthy adult female volunteers, confirming the operational feasibility of the planned dose levels. These preliminary findings support further monitored evaluation in clinically relevant populations, though longer follow-up remains necessary to assess delayed immunological or late adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1832888","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:10:40Z","timestamp":1783077040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Feasibility and safety profile of intranasal third-party allogeneic CD45RO+\/RA\u2212 memory T cells: a phase I clinical trial (vRELEASE-I NCT06699758)"],"prefix":"10.3389","volume":"13","author":[{"given":"Karima","family":"Al-Akioui-Sanz","sequence":"first","affiliation":[{"name":"CIBERER-ISCIII, IdiPAZ-CNIO Translational Research Unit in Pediatric Hemato-Oncology, La Paz University Hospital Research Institute-Spanish National Cancer 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