Human adenovirus-specific γ/δ and CD8+ T cells generated by T-cell receptor transfection to treat adenovirus infection after allogeneic stem cell transplantation.

Dörrie J, Krug C, Hofmann C, Mueller I, Wellner V, Knippertz I, Schierer S, Thomas S, Zipperer E, Printz D, Fritsch G, Schuler G, Schaft N, Geyeregger R (2014)

Publication Type: Journal article

Publication year: 2014

Journal

PLoS ONE Public Library of Science

Book Volume: 9

Pages Range: e109944

Journal Issue: 10

DOI: 10.1371/journal.pone.0109944

Abstract

Human adenovirus infection is life threatening after allogeneic haematopoietic stem cell transplantation (HSCT). Immunotherapy with donor-derived adenovirus-specific T cells is promising; however, 20% of all donors lack adenovirus-specific T cells. To overcome this, we transfected α/β T cells with mRNA encoding a T-cell receptor (TCR) specific for the HLA-A*0101-restricted peptide LTDLGQNLLY from the adenovirus hexon protein. Furthermore, since allo-reactive endogenous TCR of donor T lymphocytes would induce graft-versus-host disease (GvHD) in a mismatched patient, we transferred the TCR into γ/δ T cells, which are not allo-reactive. TCR-transfected γ/δ T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8α-encoding mRNA. In direct comparison with TCR-transfected α/β T cells, TCR-CD8α-co-transfected γ/δ T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected α/β T cells and TCR-CD8α-co-transfected γ/δ T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only α/β T cells but also γ/δ T cells can be equipped with an adenovirus specificity by TCR-RNA electroporation. Thus, our strategy offers a new means for the immunotherapy of adenovirus infection after allogeneic HSCT.

Authors with CRIS profile

Jan Dörrie Department of Dermatology Christian Krug Lehrstuhl für Genetik Christian Hofmann Lehrstuhl für Medizinische Physik und Mikrogewebetechnik Gerold Schuler Lehrstuhl für Haut- und Geschlechtskrankheiten Niels Schaft Department of Dermatology

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) St. Anna Kinderkrebsforschung AT Austria (AT)

How to cite

APA:

Dörrie, J., Krug, C., Hofmann, C., Mueller, I., Wellner, V., Knippertz, I.,... Geyeregger, R. (2014). Human adenovirus-specific γ/δ and CD8+ T cells generated by T-cell receptor transfection to treat adenovirus infection after allogeneic stem cell transplantation. PLoS ONE, 9(10), e109944. https://doi.org/10.1371/journal.pone.0109944

MLA:

Dörrie, Jan, et al. "Human adenovirus-specific γ/δ and CD8+ T cells generated by T-cell receptor transfection to treat adenovirus infection after allogeneic stem cell transplantation." PLoS ONE 9.10 (2014): e109944.

BibTeX: Download