Capture and generation of adenovirus specific T cells for adoptive immunotherapy

SummaryAdenoviral infections represent a major cause of morbidity and mortalityfollowing haematopoietic stem cell transplantation. Current anti-viral agentsare virostatic and it is evident that elimination of adenovirus (ADV) infectionis only achieved by recovery of cellular immunity. Using an interferon-gamma (IFN-c) secretion and capture assay to isolate ADV-specific T cells,followed by a 2 week expansion and restimulation protocol, we generatedADV T cells that may be used for cellular immunotherapy. In contrast tovirus-specific T cells for cytomegalovirus or Epstein-Barr virus, the ADVresponse was dominated by CD4 + T cells and the majority of captured cellsexhibited an effector/memory immunophenotype. Highly specific antigenresponses were demonstrated by intracellular IFN-c expression andcytotoxicity assays when the expanded cells underwent restimulation withADV-pulsed target cells. Although T cells were initially generated in responseto ADV species C, the expanded populations also showed strong activityagainst ADV species B, suggesting cross-reactivity across ADV species; afinding that has important clinical consequences in the paediatric setting,where the majority of infections are caused by ADV type B and C. Theprotocols can be readily translated to generate ADV-specific T cells suitablefor clinical use and offer an effective immunotherapeutic strategy to controlADV infection.Keywords: adenovirus, cellular immunotherapy, interferon-c.