Can nTregs Minimize Immunosuppression after Kidney Transplant?

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An approach using autologous natural regulatory T cells (nTregs) appears safe and feasible for minimizing immune suppression after kidney transplantation, according to a phase I/IIa clinical trial in The British Medical Journal.

The researchers report an initial experience with their “in-house” autologous CD4+CD25+FoxP3+ nTreg product in 11 living kidney donor transplant recipients. The nTreg product was administered 7 days posttransplant in a single intravenous dose of 0.5, 1.0, or 2.5 to 3.0 × 106 cells/kg. After treatment, the investigators attempted stepwise tapering of standard triple immunosuppression to low-dose tacrolimus monotherapy up to week 48.

A composite clinical and safety outcome (biopsy-confirmed acute rejection, nTreg infusion-related adverse effects, and signs of overimmunosuppression) was assessed at 60 weeks, plus an additional 3 years’ follow-up. Outcomes were compared with those of nine recipients enrolled in a previous reference trial. The study also assessed allograft functioning and an exploratory biomarker portfolio.

For all 11 enrolled patients, a 40- to 50-mL sample of peripheral blood obtained 2 weeks pretransplant yielded nTregs of sufficient yield, purity, and functionality. There were no dose-limiting toxic effects. All recipients in both trials had a functioning allograft at 3 years with similar clinical and safety outcomes.

Ten of the 11 patients receiving nTregs were successfully weaned to low-dose tacrolimus monotherapy. Two patients were switched back to standard immunosuppression due to clinical events; thus, 8 patients achieved stable monotherapy immunosuppression. Mechanistic studies suggested that nTregs reduced activation of conventional T cells, with an in vivo shift from a polyclonal to an oligoclonal T cell receptor repertoire.

Preclinical trials have suggested that adoptive transfer of nTregs might be a promising approach for tapering immunosuppression after organ transplantation. The new study adds further evidence of good clinical and safety outcomes with nTregs. The investigators conclude, “These data show stable minimisation of immunosuppression in most patients receiving nTreg treatment after kidney transplantation” [Roemhild A, et al. Regulatory T cells for minimising immune suppression in kidney transplantation: Phase I/IIa clinical trial. BMJ 2020; 371:m3734. doi: 10.1136/bmj.m3734].