• Tobias Feuchtinger, Celine Richard, Stefanie Joachim, Michael H Scheible, Michael Schumm, Klaus Hamprecht, David Martin, Gerhard Jahn, Rupert Handgretinger, and Peter Lang.
• Department of Pediatric Hematology/Oncology, University Children's Hospital, Eberhard-Karls University, Hoppe-Seyler Strasse 1, D-72076 Tuebingen, Germany. tobias.feuchtinger@med.uni-tuebingen.de
• J. Immunother. 2008 Feb 1; 31 (2): 199-206.

AbstractAdenovirus infection after allogeneic hematopoietic stem cell transplantation is still causing significant morbidity and mortality, especially in children. It has been demonstrated that a sufficient host T-cell response is essential to clear the virus. Adoptive transfer of specific T-cell immunity from the donor to the recipient has become a new treatment option for patients with systemic adenoviral infection who lack specific T-cell responses. The adenoviral hexon protein was shown to be an immunodominant T-cell target. We describe here a Good Manufacturing Practice-compatible generation of hexon-specific T cells developed by isolating interferon-gamma-secreting T cells after stimulation of mononuclear cells ex vivo with hexon protein. Phenotypical and functional characterization of the generated, specific T-cell product resulted in a mixed population of CD4 and CD8-positive T cells with an intermediate effector memory phenotype. Isolated hexon-specific T cells showed high expansion potential in vitro and specific cytotoxicity. T-cell lines, directed against type 5 hexon protein showed good crossreactivity against viral strains from other adenovirus species. The availability for isolation of hexon-specific T cells among 76 hematopoietic stem cell transplantation donors showed in > 72% a sufficient T-cell response (0.05% of T cells). In conclusion, Good Manufacturing Practice-grade selection of adenovirus-specific T cells for adoptive immunotherapy by hexon-induced secretion of interferon-gamma has been established. Adoptive T-cell transfer could potentially restore T-cell immunity against adenovirus after allogeneic stem cell transplantation.

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