Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Since T-cell immunity contributes to the control of many viral pathogens, adoptive immunotherapy with virus-specific T-cells has been a logical and effective way of combating severe viral disease in immunocompromised patients in multiple phase I and II clinical trials. Common viral targets include cytomegalovirus, Epstein-Barr virus, and adenovirus, though recent published studies have successfully targeted additional pathogens, including HHV6, BK virus and JC virus. Though most studies have utilized VSTs derived from allogenic stem cell donors, the use of banked VSTs derived from partially HLA-matched donors has shown efficacy in multi-center settings. Hence, this approach could shorten the time for patients to receive VST therapy thus improving accessibility. In this review, we discuss the usage of VSTs for patients with PID in clinical trials, as well as future potential targets and methods to broaden the applicability of virus-directed T-cell immunotherapy for this vulnerable patient population.

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