Table 1.

Clinical studies of donor-derived cytomegalovirus-specific T cells in patients after hematopoietic stem cell transplantation

Cell TherapyNo. of PatientsDate of StudyActivationAcute Graft Versus Host DiseaseDoseCytomegalovirus-related OutcomeRefa
CD8 cell clones141995Autologous fibroblasts pulsed with CMV virion proteins3 grade 1–2 GVHDIntrapatient dose escalation: range 33 × 106/m2 to 1 × 109/m2 Reconstitution CMV immunity in 14/14(36)
Polyclonal T cell lines82002CMV lysateNone1 × 107 T cells/m25/8 cleared after dose 1; 1/8 cleared after dose 2; 1/8 nonevaluable(68)
Polyclonal T cell lines162003CMV Ag-pulsed DCs3 Grade 1 skin GVHD1 × 105/kg8/16 patients did not require antiviral drugs; further reactivation in 2/16 only(38)
CD8 cells (multimer selected)92005NLV-HLA-A02 pentamers2 Grade 1–2 GVHD1.23 × 103/kg to 3.3 × 104/kg8/9 cleared viremia(69)
CD4 T cell clones252005CMV Ag1 Grade 2 GVHD1 × 105/kg to 1 × 106/kg7/25 reactivated CMV; 5/25 disease (2 died)(70)
Polyclonal T cell lines92007NLVPMVATV (HLA-A2 restricted) pulsed DCs3 Grade 3 GVHD (fatal in 1)Target dose 2 × 107/m2 Transient detection CMV-specific T cells by NLV-tetramer staining; 2/9 reactivated CMV without requirement antiviral drugs(71)
Polyclonal T cell lines122008DCs transduced with Ad5f35pp65 adenoviral vector encoding CMV-pp652 Grade 3; 2 Grade 2 GVHD2 × 107/m2 Reconstitution CMV immunity in 12/12; no requirement for antiviral drugs(72)
Polyclonal CD4 and CD8 T cells (gamma catch)182010CMV-pp65 protein1 possible GVHDMean dose 21 × 103/kg –65-specific T cellsPartial or complete viral clearance in 15/18(56)
Polyclonal CD4 and CD8 T cells (gamma catch)18 (11 preemptive, 7 prophylactic)2011Recombinant pp65 or overlapping pp65 peptide pool5 Grade 1; 2 Grade 2; 1 Grade 3 GVHDTarget dose 1 × 104/CD3 T cells/kgCMV-reactive T cells in 11/11 preemptively treated patients; 7/7 patients treated prophylactically did not reactivate CMV(73)
CD8 T cells (multimer selected)22011Peptides derived from pp65None0.37 × 105 to 2.2 × 105 CMV-pp65-CTL/kg2/2 complete responses(74)
Polyclonal T cell lines72012Peptides derived from IE-1 and pp65None2.5 × 105 to 5 × 105 CD3+CMV CTL/kg5/7 developed CMV-specific CTL activity in the blood; 2/7 no response(75)
Polyclonal CD4 and CD8 T cells (gamma catch)62012Two CMV-pp65 peptidesNone0.6 × 106 to 17 × 106 T cells (comprising 54%–96% CMV-pp65-specific CD8 T cells6/6 cleared viremia(76)
CD8 T cells (multimer selected)22012NLV-containing HLA-A02 pentamersNone0.8 × 104 to 10.8 × 104 cells/kg2/2 complete responses(77)
Polyclonal T cell lines16201515-mer peptides spanning pp65None5 × 105/kg (x 1 dose) to 1 × 106/kg (×3 weekly doses)14/16 cleared viremia (including 2 with CMV disease)(78)
  • CMV, cytomegalovirus; GVHD, graft versus host disease; Ag, antigen; DC, dendritic cell; NLV, NLVPMVATV; CTL, cytotoxic T lymphocytes; VST, virus-specific T lymphocyte.

  • a Some cited studies incorporate results of other published studies.