Aim

“ThRIL” is a multiple site, open-label, uncontrolled, phase I clinical trial assessing the safety and applicability of a CD4⁺CD25⁺FOXP3⁺ regulatory T cell (Treg) immunotherapy in the setting of liver transplantation.

Methods

Adult recipients who have received a cadaveric liver allograft are treated with a single infusion of an in vitro expanded autologous polyclonal Treg product (TR002). Three sequential cohorts of 3 patients receive a low (0.5-1 million Tregs/kg), intermediate (3-4.5 million Tregs/kg) or high (5.0-6.5 million Tregs/Kg) dose. The first cohort of patients were recruited in the pre-transplant period, with procurement of whole blood immediately pre-transplant and infusion at 13 weeks post-transplant.

Limited applicability of the original trial protocol necessitated a protocol revision to recruit stable patients 6-12 months post-transplantation with leukapheresis utilised to procure the starting material and infusion at week 16 post enrolment [Figure 1]. Patients undergo a 6-month follow up period and a comprehensive immunomonitoring program.

Results

Over an initial 12-month recruitment period under the original trial protocol 62.5% of eligible patients were enrolled. 10% of patients were withdrawn for logistical reasons, 40% for receiving allografts outside of specified criteria and 30% for clinical reasons. 7 patients remained eligible at the time of transplantation. 4 patients were subsequently withdrawn prior to infusion due to post-operative complications, failure of dose manufacture or failure to meet progression criteria.

To date 3 patients have received the low dose with no dose limiting toxicities. Target enrolment has been achieved following protocol revision with dosing of cohorts 2 and 3 scheduled for January and April 2017 respectively.

Treg therapy appears to be safe in the setting of liver transplantation but has limited applicability when used in the early post-transplant period and a strategy targeting recipients at later time points may be more clinically relevant.

CITATION INFORMATION: Whitehouse G, Safinia N, Thirkell S, Fry L, Grageda N, Martinez-Llordella M, Lechler R, Heaton N, Lombardi G, Sanchez-Fueyo A. Applicability and Safety of a Regulatory T Cell Therapy in Adult Liver Transplantation: The “ThRIL” Phase I First-in-Human Trial. Am J Transplant. 2017;17 (suppl 3).

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