Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT
Hematopoietic stem cell transplantation (HSCT) has improved over the last few decades. However, viral infections are often refractory to pharmacologic treatment and require alternative treatment strategies such as immunotherapy. Adenovirus (AdV) is th predominant disease-causing pathogen in pediatri...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 23, 2015
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| In: |
Blood
Year: 2015, Volume: 125, Issue: 12, Pages: 1986-1994 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2014-06-573725 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1182/blood-2014-06-573725 Verlag, kostenfrei, Volltext: http://www.bloodjournal.org/content/125/12/1986 
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| Author Notes: | Judith Feucht, Kathrin Opherk, Peter Lang, Simone Kayser, Lena Hartl, Wolfgang Bethge, Susanne Matthes-Martin, Peter Bader, Michael H. Albert, Britta Maecker-Kolhoff, Johann Greil, Hermann Einsele, Paul-Gerhardt Schlegel, Friedhelm R. Schuster, Bernhard Kremens, Claudia Rossig, Bernd Gruhn, Rupert Handgretinger, and Tobias Feuchtinger |
| Summary: | Hematopoietic stem cell transplantation (HSCT) has improved over the last few decades. However, viral infections are often refractory to pharmacologic treatment and require alternative treatment strategies such as immunotherapy. Adenovirus (AdV) is th predominant disease-causing pathogen in pediatric HSCT. In a clinical trial, we analyzed safety and efficacy of ex vivo adoptive T-cell transfer (ACT) with hexon-specific T cells, predominantly of the T-helper cell 1 (Th1) phenotype, in 30 patients with AdV disease or viremia. ACT was feasible with no acute toxicities or significant onset of graft-versus-host disease. ACT led to in vivo antiviral immunity for up to 6 months with viral control, resulting in complete clearance of viremia in 86% of patients with antigen-specific T-cell responses. After ACT and a follow-up of 6 months, overall survival was markedly increased in responders (mean, 122 days; 15 survivors) compared with nonresponders who all died shortly after ACT (mean, 24 days; no survivors). AdV-related mortality was 100% in nonresponders compared with 9.5% in responders (≥1 log reduction of DNA copies per milliliter after ACT). In summary, ex vivo ACT of AdV-specific Th1 cells was well tolerated and led to successful and sustained restoration of T-cell immunity correlated with virologic response and protection from virus-related mortality. This cellular immunotherapy is a short-term available and broadly applicable treatment. The study is registered at European Union Clinical Trials Register as 2005-001092-35. |
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| Item Description: | Gesehen am 28.08.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2014-06-573725 |