Virus-specific T-cell therapies for patients with primary immune deficiency.
Publication Year:
2020
PubMed ID:
31942610
Funding Grants:
Public Summary:
Viral infections are common and are potentially life-threatening in patients with immune system disorders. Because immune cells (T-cells) contributes to the control of many viral infections, treatment with virus-specific T cells (VSTs) has been an effective way of combating severe viral disease in immunocompromised patients in prior studies. Common viral targets include cytomegalovirus, Epstein-Barr virus, and adenovirus, though recent published studies have successfully targeted additional infections, including HHV6, BK virus, and JC virus. Though most studies have used VSTs derived from bone marrow transplant donors, the use of pre-made VSTs from other healthy donors has shown efficacy in several studies. This approach could improve the accessibility of this therapy. In this review, we discuss the usage of VSTs for patients with primary immunodeficiency disorders 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.
Scientific Abstract:
Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Because T-cell immunity contributes to the control of many viral pathogens, adoptive immunotherapy with virus-specific T cells (VSTs) has been a logical and effective way of combating severe viral disease in immunocompromised patients in multiple phase 1 and 2 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 used VSTs derived from allogenic stem cell donors, the use of banked VSTs derived from partially HLA-matched donors has shown efficacy in multicenter 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 primary immunodeficiency disorders 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.