Doerrie, Jan and Krug, Christian and Hofmann, Christian and Mueller, Ina and Wellner, Verena and Knippertz, Ilka and Schierer, Stephan and Thomas, Simone and Zipperer, Elke and Printz, Dieter and Fritsch, Gerhard and Schuler, Gerold and Schaft, Niels and Geyeregger, Rene (2014) Human Adenovirus-Specific gamma/delta and CD8(+) T Cells Generated by T-Cell Receptor Transfection to Treat Adenovirus Infection after Allogeneic Stem Cell Transplantation. PLOS ONE, 9 (10): e109944. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)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 alpha/beta 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 gamma/delta T cells, which are not allo-reactive. TCR-transfected gamma/delta T cells secreted low quantities of cytokines after antigen-specific stimulation, which were increased dramatically after co-transfection of CD8 alpha-encoding mRNA. In direct comparison with TCR-transfected alpha/beta T cells, TCR-CD8 alpha-co-transfected gamma/delta T cells produced more tumor necrosis factor (TNF), and lysed peptide-loaded target cells as efficiently. Most importantly, TCR-transfected alpha/beta T cells and TCR-CD8 alpha-co-transfected gamma/delta T cells efficiently lysed adenovirus-infected target cells. We show here, for the first time, that not only alpha/beta T cells but also gamma/delta 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TCR GENE-TRANSFER; GAMMA-DELTA; ADOPTIVE IMMUNOTHERAPY; DENDRITIC CELLS; VIRAL-INFECTIONS; IFN-GAMMA; LYMPHOCYTES; ANTIGEN; RNA; CANCER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2019 08:21 |
| Last Modified: | 12 Aug 2019 08:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9362 |
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