Abstract |
Adoptive immunotherapy against viral infections is a promising treatment option for patients after hematopoietic stem cell transplantation. However, the generation of virus-specific T cells is either cost-intensive or time-consuming. We developed the first GMP-compliant protocol to generate donor-derived adenovirus (HAdV), cytomegalovirus, and Epstein-Barr virus-specific T-cell lines (TCLs) within 12 days by the use of overlapping polypeptides derived from different viruses in combination with IL-15. Two patients after undergoing haploidentical hematopoietic stem cell transplantation with HAdV viremia displaying rising viral loads despite treatment with cidofovir received 1×10 donor-derived short-term expanded HAdV-specific TCLs per kg body weight. In both patients, HAdV-specific T cells could be detected by IFN-γ-ELISpot 30 and 22 days postinfusion, and resulted in complete clearance or >1.5 log reduction of viral load within 15 and 18 days, respectively. This protocol facilitates rapid and cost-effective generation of virus-specific TCLs, which appear to provide an effective treatment option.
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Authors | René Geyeregger, Christine Freimüller, Julia Stemberger, Michaela Artwohl, Volker Witt, Thomas Lion, Gottfried Fischer, Anita Lawitschka, Julia Ritter, Michael Hummel, Wolfgang Holter, Gerhard Fritsch, Susanne Matthes-Martin |
Journal | Journal of immunotherapy (Hagerstown, Md. : 1997)
(J Immunother)
Vol. 37
Issue 4
Pg. 245-9
(May 2014)
ISSN: 1537-4513 [Electronic] United States |
PMID | 24714358
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adenovirus Infections, Human
(immunology, therapy, virology)
- Adenoviruses, Human
(classification, immunology)
- Child, Preschool
- Fatal Outcome
- Female
- Graft vs Host Disease
(etiology)
- Hematopoietic Stem Cell Transplantation
(adverse effects)
- Humans
- Immunotherapy, Adoptive
(methods, standards)
- Infant
- Male
- Peptides
(pharmacology)
- T-Cell Antigen Receptor Specificity
(immunology)
- T-Lymphocytes
(drug effects, immunology, transplantation)
- T-Lymphocytes, Cytotoxic
(drug effects, immunology, transplantation)
- Transplantation, Homologous
- Treatment Outcome
- Viral Load
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