Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells.
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-gamma 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.
Moosmann
Andreas
A
Clinical Cooperation Group Molecular Oncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität, Munich, Germany. andreas.moosmann@helmholtz-muenchen.de
Bigalke
Iris
I
Tischer
Johanna
J
Schirrmann
Leah
L
Kasten
Julitta
J
Tippmer
Stefanie
S
Leeping
Marina
M
Prevalsek
Dusan
D
Jaeger
Gundula
G
Ledderose
Georg
G
Mautner
Josef
J
Hammerschmidt
Wolfgang
W
Schendel
Dolores J
DJ
Kolb
Hans-Jochem
HJ
D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy / Q000821:virology; D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000628:therapy*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma; D007937:Leukapheresis / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy / Q000821:virology; D017710:Lymphocyte Transfusion; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous; D014764:Viral Proteins / Q000276:immunology / Q000494:pharmacology*
D000956:Antigens, Viral; D010455:Peptides; D014764:Viral Proteins; D007371:Interferon-gamma