Third-Party Viral Specific T Cells for Immunocompromised Hosts and Access Barriers: A Review and Commentary by an Expert Panel from ASTCT

Viral reactivation is a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT), particularly in the setting of intensified graft-versus-host disease prophylaxis using in vivo or ex vivo T-cell depletion. Reactivation of BK virus, JC virus, adenovirus, and other opportunistic pathogens is especially problematic, as effective FDA-approved antiviral therapies are limited or unavailable, with pediatric recipients being at particular risk. Virus-specific T-cells (VSTs) represent a compelling immunotherapeutic strategy to restore antiviral immunity and control refractory viral infections after HCT. However, VSTs are not currently FDA-approved in the United States and are accessible only at a small number of academic centers under investigational new drug oversight, limiting their broader clinical impact. In this review, we convened a panel of experts to summarize the current landscape of VST therapy, including clinical indications, efficacy, and safety outcomes across multiple viral targets. We also identify key challenges in the field, including regulatory barriers, manufacturing scalability, product standardization, and distribution. Finally, we discuss potential strategies to facilitate more reliable and equitable access to VSTs, including collaborative manufacturing models and alternative regulatory pathways, with the goal of integrating these therapies more broadly into post-transplant care.