Adoptive Transfer of Hexon-Specific T-Cells as a Treatment of Adenovirus Reactivation Following Allogeneic Stem Cell Transplantation.

Abstract 796

In pediatric patients human adenovirus (HAdV) was identified as a common viral pathogen responsible for significant morbidity and mortality post allo SCT. Antiviral chemotherapy is often insufficient. Given that T-cell immunity is crucial for protection against adenoviral infection/reactivation, cellular immunotherapy is a promising therapeutic option. The capsid protein Hexon has been shown to contain immunodominant T-cell epitopes, with T-cell responses in the majority of the healthy population. Therefore a prospective phase I/II clinical study was performed analysing safety and feasibility of adoptive Hexon-specific T-cell transfer in patients after allogeneic SCT and HAdV infection refractory to Cidofovir treatment. Hexon-specific T-cells were isolated from the SCT-donor by using the IFNγ secretion system and small T-cell populations were immediately infused, without in vitro expansion steps. Fourty pediatric and adult patients with a mean age of 15 years were treated according to the study protocol after haploidentical, matched unrelated and matched sibling donor SCT between day 11 and 327 post SCT. The T-cell dose varied from 300-25000 T-cells/kg. No acute toxicitiy was observed. In two patients GvHD °I-°II of the skin occured within two weeks after administration of specific T-cells, one patient also developed GvHD of the gut. In vivo T-cell responses were absent in all patients before adoptive T-cell transfer and detectable in 70% of evaluable patients within the first weeks after adoptive transfer, associated with a clinical and/or virological response to the adoptive T-cell transfer. However, in patients with adenoviral disease response rate was lower and 6 of 14 evaluable patients succumbed with the infection within few days, in spite of adoptive immunotherapy. This lead to the assumption, that adoptive treatment in patients with severe infection related morbidity was to late during the course of infection. In conclusion we could show that adoptive immunotherapy is safe, feasible and a promising therapeutic option in patients with HAdV infection. Infusion of small IFNγ producing Hexon-specific T-cells populations resulted in an in vivo expansion of specific T-cells in the majority of cases. Emergence of in vivo T-cell responses was closely associated with a clearance or reduction of the viral load.