Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation

Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation
Severe viral infection post HSCT are still a major cause of morbidity and mortality. Current antivirals can be ineffective and associated with significant toxicities. Donor-derived virus-specific T cells (VSTs) have been shown to be efficacious but issues include high costs, complex manufacturing and the need of seropositive donors. This study aimed to study VSTs generated from eligible, third-party donors.
Phase 2 study using generated banks of VSTs that recognized five common viral pathogens: EBV, adenovirus (AdV), CMV, BK virus, and human herpesvirus 6.
38 patients with 45 drug-refractory infections received the VST +/- antivirals depending on physician preference. A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed.
Small, single centre, adult study thus unknown if these results can be replicated in pediatric HSCT patients. Not an RCT.
New methods to decreased morbidity and mortality associated with viral infections post HSCT are needed and banked VSTs may be a feasible, safe, and effective approach but more studies needed, in particular RCTs on paediatric populations.

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