. Author manuscript; available in PMC: 2022 Dec 1.

Published in final edited form as: Transplantation. 2021 Dec 1;105(12):e303–e321. doi: 10.1097/TP.0000000000003765

Table 2.

Clinical trials of adoptive transfer of regulatory macrophages in solid organ transplantation.

Trial (center)	Study	Patients	Cell and dosing	Immunosuppression protocol	Outcomes	References
*The ONE study* Mreg trial (University of Regensburg)	Phase I/II clinical trial N = 8 enrolled N = 2 treated	Living donor kidney transplant Immunological risk: first graft, at least 1/6 HLA mismatch, PRA < 40%, did not need desensitization	Allogeneic (donor-derived) CD14+ peripheral blood monocytes co-cultured with low dose M-CSF with IFNγ stimulation on day 6 for 24hr. Dose: 2.5–7.5×10⁶ cells/kg infused 7 days prior to transplantation	Cell infusion (intervention group) or basiliximab (reference group). Prednisolone tapered off before 20 weeks. Tacrolimus continued throughout the study with target levels specified in keeping with ELITE-Symphony trial. MPA continued until study end but if in cell therapy group, there was an option for deliberate dose tapering from 36-weeks if no evidence of rejection.	Pooled data for CTG of autologous tolerogenic DCs, Mreg and Tregs Primary endpoint – biopsy proven rejection. Result: no difference between the groups. Secondary endpoint – histological changes of rejection without clinical evidence, eGFR. Result: no difference and CTG also found to have higher population of Tregs and less viral infections compared to reference trial group	Sawitzki B et al, 2020¹⁰⁴ NCT02085629
Regulatory macrophages (University of Regensburg)	Pilot study N = 5	Living donor kidney transplant Immunological risk: first graft, did not need desensitization, anti-HLA Ab < 5%	Donor-derived CD14+ peripheral blood monocytes cultured with low dose M-CSF with IFNγ stimulation Dose: 1.74–10.39×10⁷ cells/kg on day 5 post transplantation	Induction with antithymocyte globulin, tacrolimus and corticosteroids. Steroids weaned by day 14 if no concerns for rejection and physician had option to wean down tacrolimus dose if nil rejection on first protocol biopsy at 8 weeks.	Primary outcome: biopsy-proven rejection. 4 of 5 patients were able to be maintained on low dose tacrolimus One biopsy proven rejection in context of low tacrolimus levels (2–4 ng/ml)	Hutchinson J et al, 2008¹⁰⁵
Regulatory macrophages (Mreg)	Pilot study N = 10	Deceased donor kidney transplant Immunological risk: first graft, all HLA mismatch groups allowed	Donor-derived, CD14+ monocytes cultured with low dose M-CSF with IFNγ stimulation on day 6, ready for use by day 7 culture Dose: 1.37–9×10⁷ cells/kg administered 5 days post transplantation	Induction with tacrolimus, sirolimus, and corticosteroids. Steroids and sirolimus were weaned over the duration of the study	Primary outcome: biopsy-proven rejection. 7 of the 10 patients who received Mreg suffered confirmed (or suspected) rejection episodes between 6–28 weeks post transplantation.	Hutchinson J et al, 2008¹⁰⁶

Ab, antibody; CTG, cell therapy group; DC, dendritic cell; eGFR, estimated glomerular filtration rate; IFNγ, interferon gamma; M-CSF, macrophage colony stimulating factor; MPA, mycophenolic acid; Mreg, regulatory macrophage; PRA, plasma renin concentration; Treg, regulatory T cell.