Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation.
Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral immunity after SCT and could protect from CMV-related complications. However, logistics of producing virus-specific T-cell grafts limited the clinical application. We treated 18 patients after allo-SCT from human leukocyte antigen-mismatched/haploidentical or human leukocyte antigen-matched unrelated donors with polyclonal CMV-specific T cells generated by ex vivo stimulation with pp65, followed by isolation of interferon-γ-producing cells. Patients with CMV disease or viremia refractory to antiviral chemotherapy or both were eligible for adoptive T-cell transfer and received a mean of 21 × 10³/kg pp65-specific T cells. In 83% of cases CMV infection was cleared or viral burden was significantly reduced, even in cases of CMV encephalitis (n = 2). Viral control was associated with in vivo expansion of CMV-specific T lymphocytes in 12 of 16 evaluable cases, resulting in reconstitution of antiviral T-cell responses, without graft-versus-host disease induction or acute side effects. Our findings indicate that the infusion of low numbers of CMV-specific T cells is safe, feasible, and effective as a treatment on demand for refractory CMV infection and CMV disease after allo-SCT.
Feuchtinger
Tobias
T
Department of Pediatric Hematology/Oncology, University Children's Hospital, Tübingen, Germany. obias.feuchtinger@med.uni-tuebingen.de
Opherk
Kathrin
K
Bethge
Wolfgang A
WA
Topp
Max S
MS
Schuster
Friedhelm R
FR
Weissinger
Eva M
EM
Mohty
Mohamad
M
Or
Reuven
R
Maschan
Michael
M
Schumm
Michael
M
Hamprecht
Klaus
K
Handgretinger
Rupert
R
Lang
Peter
P
Einsele
Hermann
H
D000293:Adolescent; D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D012008:Recurrence; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D013997:Time Factors; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000276:immunology*
D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa