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Table 1 Clinical evidence for adoptive transfer of CMV-specific T cells

From: Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation

Reference Method No. of patients Results Dose
In vitro stimulation and expansion
Riddell et al. (1992) [22] Allogeneic CMV-spec. CD8+ clones 3 3/3 prevention of viremia and pneumonia 3.3 × 107–109 cells/m2
Walter et al. (1995) [45] Allogeneic CMV-spec. CD8+ clones phase I 14 (11) 11/11 prevention of CMV infection 3.3 × 107–109 cells/m2
Einsele et al. (2002) [23] Allogeneic CMV-spec. polyclonal CD8+ and CD4+ T cells 8 5/7 evaluable patients eliminated infection 107 cells/m2
Peggs et al. (2003) [46] Allogeneic CMV-specific polyclonal CD8+ and CD4+ T cells 16 14/16 no viral reactivation, reconstitution of antiviral immunity 105 cells/kg
Perruccio et al. (2005) [56] Allogeneic CMV-specific CD4+ clones 25 prophylaxis 7/25 patients had CMV-reactivation, 5/25 patients developed CMV-disease (3 eliminated infection) 105–3 × 106 cells/kg
Meji et al. (2012) [57] CMV-specific polyclonal CD8+ and CD4+ T cells phase I/II 6 6/6 patients eliminated infection 0.9 × 104–3.1 × 105 cells/kg
Pei et al. (2017) [58] CMV-specific cytokine induce effector cells phase I 32 27/32 responded 0.66–15.41 × 107 CD8+ and 0.68–9.25 × 105 CD4+
Withers et al. (2017 and 2018) [55, 59] CMV-specific third-party CD8+ and CD4+ T cells phase I 27 26/27 responded 1.37–5.0 × 107 cells/m2
Direct isolation via peptide-HLA multimers
Cobbold et al. (2005) [47] Allogeneic CMV-specific CD8+ T cells using MHC-I-tetramers 9 8/9 patients eliminated infection 1.2–33 × 103 cells/kg
Schmitt et al. (2011) [48] Allogeneic CMV-specific CD8+ T cells using MHC-I-streptamers 2 2/2 control of CMV-viremia 0.37 and 2.2 × 105 cells/kg
Uhlin et al. (2012) [60] Allogeneic CMV-specific CD8+ T cells using MHC-I-pentamers 5 4/5 responders 0.8–24.6 × 104 cells/kg
Blyth et al. (2013) [61] Allogeneic CMV-specific polyclonal CD8+ and CD4+ T cells phase II 50 Prophylaxis 41/50 did not require CMV-directed pharmacotherapy 2 × 107 cells/m2
Neuenhahn et al. (2017) [12] Allogeneic CMV-specific CD8+ T cells using MHC-I-streptamers phase I/IIa 16 Stem cell donor-derived: 7/7 responders third-party transfer: 5/8 responders 6.3 × 106 cells (HSCT donor) 1.4 × 107 cells (third-party donor)
Direct isolation via cytokine-capture technique
Feuchtingeret al. (2010) [28] CMV-specific polyclonal CD8+ and CD4+ T cells 18 15/18 responders 1.2–166 × 103 cells/kg
Peggs et al. (2011) [62] CMV-specific polyclonal CD8+ and CD4+ T cells phase I/II 18 Prophylaxis: 6/7 virus-free Pre-emptive: 2/11 required no antiviral drug treatment Median: 3.5 × 104 cells/kg
Kàllay et al. (2018) [43] CMV-specific polyclonal CD8+ and CD4+ T cells 3 2/3 viral clearance 1/3 decrease in viral load 7.5–16.2 × 104 cells/kg