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-␥-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 ؋ 10 3 /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

Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis

“…11 The use of CD45RA À memory T cells in adoptive immunotherapy could also circumvent the technically much more complex and pathogen-restricted ex vivo selection of pathogen-specific donor T cells by HLA-peptide multimers or cytokine secretion assays. 12,13 The absolute numbers of pathogen-reactive IFN-g spot-forming cells were overall not increased in CD45RA -memory T cells compared with original LPs. Potential reasons for this observation are the depletion-induced variation in CD4/CD8 ratio as well as the removal of late effector T cells.…”

Umbilical cord blood graft engineering: challenges and opportunities

“…88,89 Rapid isolation strategies such as 'gamma catch' can be utilized when VSTs occur at high frequency in the donor's blood. This strategy has been successfully used in patients with CMV disease or viremia, with a response rate of 83%, 90 EBV, with a response rate of 50-70% 91,92 and ADV, with responses in 5 of 6 patients in a small study. 93 Adoptive transfer of VSTs from an adult stem cell donor is effective as prophylaxis and treatment for treatment-refractory EBV, CMV and ADV infections.…”

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

“…Techniques for direct selection of VSTCs include the use of peptide pools derived from viral antigens to expand T cells with multiple antigen specificities [97], the selection of VSTCs based upon the secretion of interferon-gamma (IFN-gamma) [98,99] or the binding to class I HLA-multimers [100] or immunomagnetic beads [101]. The multimer selection method requires HLA-specific elements for every viral epitope and is actually restricted to CD8+ T-cells, while the IFN-gamma secretion technique is based upon a HLAunrestricted selection of CD4+ and CD8+.…”