Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells

Andreas Moosmann, Iris Bigalke, Johanna Tischer, Leah Schirrmann, Julitta Kasten, Stefanie Tippmer, Marina Leeping, Dušan Prevalšek, Gundula Jaeger, Georg Ledderose, Josef Mautner, Wolfgang Hammerschmidt, Dolores J. Schendel, Hans Jochem Kolb

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available in urgent clinical situations, we developed a rapid protocol for their isolation by overnight stimulation of donor blood cells with peptides derived from 11 EBV antigens, interferon-γ surface capture, and immunomagnetic separation. Six patients with PTLD received 1 transfusion of EBV-specific T cells. No response was seen in 3 patients who had late-stage disease with multiorgan dysfunction at the time of T-cell transfer. In 3 patients who received T cells at an earlier stage of disease, we observed complete and stable remission of PTLD. Two patients have remained free from EBV-associated disease for more than 2 years. CD8+ T cells specific for EBV early antigens rapidly expanded after T-cell transfer, temporarily constituted greater than 20% of all peripheral blood lymphocytes, and were maintained throughout the observation period. Thus, a rapid and sustained reconstitution of a protective EBV-specific T-cell memory occurred after the infusion of small numbers of directly isolated EBV-specific T cells.

Original languageEnglish
Pages (from-to)2960-2970
Number of pages11
JournalBlood
Volume115
Issue number14
DOIs
StatePublished - 8 Apr 2010
Externally publishedYes

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