Adoptive transfer of third‐party donor CMV‐specific T cells for refractory cytomegalovirus infection following umbilical cord blood transplantation

Summary Refractory cytomegalovirus (CMV) infection is a severe complication following umbilical cord blood transplantation (UCBT). Antiviral agents, the standard first‐line therapy, are limited by toxicity and resistance without robust T‐cell immunity. We evaluated third‐party donor (TPD)‐derived CMV‐specific T cells (CMVSTs) as a treatment option. In a prospective phase I trial, UCBT recipients under 60 years with refractory CMV infection were enrolled. CMV‐seropositive TPDs, matched for at least one human leucocyte antigen (HLA) class I allele at high resolution, were selected from family members. CMVSTs were manufactured for two infusions within 1 month. Safety and feasibility were primary end‐points while efficacy and immune reconstitution were secondary end‐points. Ten patients (median age: 15.5 years, range: 3–46 years) received CMVSTs (median doses: 2.2 × 10 7 /m 2 and 4.2 × 10 7 /m 2 ). Products showed high CD3 + T‐cell purity and memory T‐cell dominance. Infusions caused mild adverse events, with no severe toxicities. At 6 months post‐first infusion, 80% (8/10) achieved durable virological clearance; 60% (6/10) survived at 2 years with sustained CMV control. TPD‐derived CMVST infusions are safe and feasible for refractory CMV infection post‐UCBT, offering durable virological control while larger studies are needed to confirm efficacy. This trial was registered at www.chictr.org.cn as # ChiCTR2000034951.