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Generation of a multipathogen-specific T-cell product for adoptive immunotherapy based on activation-dependent expression of CD154

Khanna, Nina and Stuehler, Claudia and Conrad, Barbara and Lurati, Sarah and Krappmann, Sven and Einsele, Hermann and Berges, Carsten and Topp, Max S.. (2011) Generation of a multipathogen-specific T-cell product for adoptive immunotherapy based on activation-dependent expression of CD154. Blood, Vol. 118, H. 4. pp. 1121-1131.

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Official URL: http://edoc.unibas.ch/dok/A6005485

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Abstract

Viral and fungal infections remain a leading cause of mortality in patients after hematopoietic stem cell transplantation (HSCT). Adoptive transfer of multipathogen-specific T cells is promising in restoring immunity and thereby preventing and treating infections, but approaches are currently limited because of time-consuming and laborious procedures. Therefore, we investigated a new strategy to simultaneously select T cells specific for viral and fungal pathogens based on activation-dependent expression of CD154. Single- and multipathogen-specific T-cell lines with high specificity for adenovirus (AdV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), Candida albicans, and/or Aspergillus fumigatus could be readily generated within 14 days irrespective of the precursor frequency. The T-cell lines responded reproducibly to endogenously processed antigen and specifically proliferated upon antigenic stimulation. Although isolation based on CD154 favors enrichment of CD4(+) T cells, AdV-, EBV- and CMV-specific CD8(+) T cells could be expanded and demonstrated lysis of target cells. Conversely, T cell-mediated alloreactivity was almost abrogated compared with the starting fraction. This selection and/or expansion strategy may form the basis for future adoptive immunotherapy trials in patients at risk for multiple infections and may be translated to other antigens.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Infektiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Infektiologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Infection Biology (Khanna)
UniBasel Contributors:Khanna, Nina
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Hematology
ISSN:1528-0020
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:44
Deposited On:06 Dec 2013 09:36

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