Purpose:

Treg therapy can reverse established inflammation in animal models. We conducted a pilot safety & feasibility trial of Treg therapy for subclinical kidney transplant inflammation.

Methods:

Peripheral blood CD4⁺CD25⁺CD127^lo/- Tregs were isolated (FACS) & polyclonally expanded ex vivo in medium containing deuterated glucose. 320×10⁶ Tregs were infused into kidney transplant recipients with subclinical inflammation on 6-m protocol biopsy. Levels of infused (labeled) Tregs in circulation were tracked by measuring deuterium using GC-MS. Inflammation was assessed on follow-up biopsies using Banff scoring and leukocyte common antigen positive (LCA⁺) cell density. Urine was assayed for common rejection module (uCRM), a biomarker of rejection.

Results:

3 transplant recipients on tac/MMF/prednisone received Treg infusions and have completed 1 year of follow up. Tregs expanded >100-fold & met all release criteria for infusion. One patient had transient lymphopenia (day 4-21) post-infusion. No infusion reactions or infections were seen & graft function remained stable. Infused Tregs peaked within week 1, making up to 7.5% of all circulating Tregs and their pharmacokinetics was similar to that seen in non-immunosuppressed patients (figure). Graft inflammation & uCRM scores improved (table and figure).

Conclusions:

It is feasible to isolate & expand Tregs from transplanted patients. Infused Tregs were well tolerated & had pharmacokinetics similar to those seen in non-immunosuppressed patients. Modulation of graft inflammation was seen post-infusion. CTOT-21 will further test the efficacy of Tregs for control of graft inflammation.

CITATION INFORMATION: Chandran S, Tang Q, Sarwal M, Laszik Z, Putnam A, Sigdel T, Tavares E, Bluestone J, Vincenti F. Infusion of Polyclonal Tregs Modulates Subclinical Kidney Transplant Inflammation: Final Report of TASK Pilot Trial. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress