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First-in-man clinical results with good manufacturing practice (GMP)-compliant polypeptide-expanded adenovirus-specific T cells after haploidentical hematopoietic stem cell transplantation.

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.
AuthorsRené 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
JournalJournal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 37 Issue 4 Pg. 245-9 (May 2014) ISSN: 1537-4513 [Electronic] United States
PMID24714358 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Peptides
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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