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Cellular Therapy

Human AdV-specific T cells: persisting in vitro functionality despite lethal irradiation

Bone Marrow Transplantation volume 49, pages 934–941 (2014)Cite this article

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Abstract

Viral infections caused by human adenovirus (HAdV) or CMV remain life-threatening complications in immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. Adoptive immunotherapy with virus-specific T cells showed impressive clinical results without or with only mild GvHD. However, because of high costs and high regulatory barriers, these protocols are accessible to only a few centers. The infusion of unmanipulated donor lymphocytes (DLIs) that contain virus-specific T cells is not feasible because of the risk of GvHD. Reports about three patients treated with irradiated granulocytes or DLIs that potentially comprised virus-specific T cells discussed an active role of virus-specific lymphocytes despite irradiation, but real evidence could not be provided. Therefore, we tested the effect of irradiation on HAdV-specific T cells, which had been expanded in vitro, by stimulating PBMCs with HAdV-peptide pools and IL-15 for 12 days. Cells were then irradiated with 30 Gy, as performed for normal granulocyte concentrates. Cell viability and polyfunctional activity were determined by flow cytometry. Even 48 h after irradiation, 15.6% of expanded HAdV-specific T cells were apparently viable and cytolytically active. Although the in vivo antiviral activity was not tested, these data support earlier assumptions about the potential role of irradiated cells in patients.

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Acknowledgements

We thank M Zavadil for carefully proofreading and language editing the manuscript. The work was funded by the Children’s Cancer Research Institute (CCRI).

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Authors and Affiliations

  1. Department of Clinical Cell Biology and FACS Core Unit, Children's Cancer Research Institute (CCRI), Vienna, Austria

    R Geyeregger, C Freimüller, J Stemberger & G Fritsch

  2. Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria

    G Fischer

  3. Department of Apheresis/Infusion Unit, St. Anna Children's Hospital, Vienna, Austria

    V Witt

  4. Department of Pediatrics, Medical University of Vienna, Vienna, Austria

    G Fritsch

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  1. R Geyeregger
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Correspondence to R Geyeregger.

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Geyeregger, R., Freimüller, C., Stemberger, J. et al. Human AdV-specific T cells: persisting in vitro functionality despite lethal irradiation. Bone Marrow Transplant 49, 934–941 (2014). https://doi.org/10.1038/bmt.2014.86

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