Frontiers in medicine · 2026
Feasibility and safety profile of intranasal third-party allogeneic CD45RO+/RA- memory T cells: a phase I clinical trial (vRELEASE-I NCT06699758).
Клиническое исследованиеСтатьяНазвание и аннотация: Перевод в очереди
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Al-Akioui-Sanz Karima, Dueñas Lopez Fiorela C, Guijarro-Eguinoa Javier, Gómez Lopez De Las Huertas Arturo, Lázaro Paula, Gasior Mercedes, Pertíñez Lidia, Clares Villa Laura, Mestre Durán Carmen, Borobia Alberto M, Balas Antonio, Calvo Cristina, Pérez-Martínez Antonio
Аннотация
BACKGROUND: 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.
METHODS: 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+/RA- 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 × 106, 5 × 106, and 10 × 106 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 in situ hybridization (FISH).
RESULTS: 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 × 106 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.
CONCLUSION: In this first-in-human, single-center phase I dose-escalation study, intranasal administration of third-party, ready-to-use, allogeneic CD45RO+/RA- 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.
METHODS: 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+/RA- 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 × 106, 5 × 106, and 10 × 106 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 in situ hybridization (FISH).
RESULTS: 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 × 106 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.
CONCLUSION: In this first-in-human, single-center phase I dose-escalation study, intranasal administration of third-party, ready-to-use, allogeneic CD45RO+/RA- 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.