title: Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Children's Hospital, Tübingen, Germany. obias.feuchtinger@med.uni-tuebingen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Kathrin
authors.initials: K
authors.lastname: Opherk
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.forename: Max S
authors.initials: MS
authors.lastname: Topp
authors.forename: Friedhelm R
authors.initials: FR
authors.lastname: Schuster
authors.forename: Eva M
authors.initials: EM
authors.lastname: Weissinger
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Michael
authors.initials: M
authors.lastname: Maschan
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Klaus
authors.initials: K
authors.lastname: Hamprecht
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
mesh_terms: 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*
chemical_list: D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa