. 2020 Nov;357:None. doi: 10.1016/j.cellimm.2020.104214

Table 2.

Published studies of expanded Treg adoptive transfer. MACS, magnetic bead sorted; FACS, fluorescence activated cell sorting, bw – body weight.

Year	n	Clinical setting	Phase	Method of Treg Generation	Culture duration (days)	Cell number (per infusion)	Poly/Allo Tregs	Treg Purity	Efficacy	Adverse Events	Ref
2009	2	GVHD after HSCT	I	Autologous MACS-sorted CD4⁺CD25⁺CD127^- 2:1 αCD3/αCD28 beads 1000U/mL IL-2	Up to 21	1. 1 × 10⁵cells/ kg bw (single infusion) 2. 3 × 10⁶ cells/ kg bw (three infusions)	Poly	1. 90% 2. 40–90%	1. Improvement in cGVHD, immunosuppression minimised. 2. Transient stabilisation of aGVHD during infusions	Patient 1. None reported Patient 2. Death (from aGVHD after completing course of Tregs)	[63]
2011	23	Prevention of GVHD after HSCT	I	Partially HLA-matched UCB MACS-sorted CD4⁺CD25⁺ 3:1 αCD3/αCD28 beads 300U/mL IL-2	18 ± 1 days	1–30 × 10⁵ cells/kg bw (9/23 single infusion, 14/23 two infusions)	Poly (donor-derived)	31–96% (median 64%)	Similar disease free survival & donor engraftment, 30% reduction in aGVHD cf. historical controls.	No dose-limiting toxicity. Hypertension in 3/23 No ↑ infection/relapse cf historical controls	[64]
2012	10	Newly diagnosed T1DM	I	Autologous FACS-sorted CD4⁺CD25⁺CD127^- 1:1 αCD3/αCD28 beads 1000U/mL IL-2	Up to 14	10–20 × 10⁶ Treg/kg bw	Poly	90–97%	Reduction in exogenous insulin requirement and HbA1c after 2 weeks, sustained to 4 months	No serious infections, acute glucose dysregulation or adverse effects	[62]
2015	14	Newly diagnosed T1DM	I	Autologous FACS-sorted CD4⁺CD25⁺CD127^- 1:1 αCD3/αCD28 beads 300U/mL IL-2 100 ng/mL rapamycin	14	5 × 10⁶ to 2.6 × 10⁹ cells (single infusion)	Poly	76–97%	No discernable effect upon c-peptide, HbA1c or insulin use	No infusion reactions No infection/malignancy during follow-up 2/16 did not reach release criteria	[65]
2016	10	Living Donor Liver Transplantation	I/IIa	Allo-stimulated PBMC CD80 and CD86 blockade No IL-2/rapamycin	14	0.23–6.4 × 10⁶ Treg /kg bw (single infusion)	Allo	3–45% (median 10%)	7/10 successfully weaned from IS (3/10 - acute rejection)	Alopecia in 1/10 CMV hepatitis in 1/10	[66]
2017	3	Renal transplantation	I	Autologous FACS-sorted CD4⁺CD25⁺CD127^- αCD3/αCD28 beads 300U/mL IL-2	14	320 × 10⁶ polyclonal Treg (single infusion)	Poly	>93%	Improvement in inflammation in 2/3, progression to cellular rejection in 1/3	No infusion reactions No patient or graft loss No infection/malignancy during 12 m follow-up	[58]
2018	9	Living Donor Renal Transplantation	I	Autologous MACS-sorted CD4⁺CD25⁺ 4:1 (later 1:1) αCD3/αCD28 1000U/mL IL-2, 1ug/mL TGF-β 100 ng/ml rapamycin	21	0.5–5 × 10⁹ Treg (single infusion)	Poly	>80% (FOXP3 expression)	Subclinical C4d + rejection in 1/9. DSA in 2/9. Recurrence of FSGS in 1/9	No adverse events	[5]
2019	9	Liver transplantation	I/IIa	Autologous MACS-sorted CD4⁺CD25⁺ 2:1 αCD3/αCD28 beads 500U/mL IL-2 100 nM rapamycin	24 – 36	0.5–4.5 × 10⁶ Treg/kg (65–468 × 10⁶ Treg infused)	Poly	61–92%	↓ donor-specific responses in those receiving highest dose of Tregs	No adverse events in low-dose Tregs infusion 1/6 transient pyrexia, leucopenia & graft dysfunction (high-dose)	[57], [61]‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬
2020	12	Living donor renal transplantation	I	Autologous MACS-sorted CD4⁺CD25⁺ 4:1 αCD3/αCD28 beads 500U/mL IL-2 100 nM rapamycin	36	1 – 10 × 10⁶ Treg/kg bw (single infusion)	Poly	Not yet reported	Not reported	No adverse events	[6], [8]