*Purpose: Low dose interleukin-2 (LDIL-2) is capable of expanding endogenous CD4+CD25+FoxP3+ regulatory T-cells (Tregs) in vivo but its role in human solid organ transplantation is unclear. We investigated the effects of LDIL-2 treatment in liver transplant (LT) recipients under calcineurin inhibitors and its capacity to promote the complete discontinuation of maintenance immunosuppression.

*Methods: ‘LITE’ is an open-label, activity, safety and efficacy, prospective single arm clinical trial in which stable LT recipients <50 years old and 2-6 years post-LT receive 1 million IU s.c. injections of IL-2 daily for up to 6 months. After 4 weeks of LDIL-2 treatment, recipients with >2-fold increase in circulating Tregs and no subclinical rejection in a liver biopsy initiate weaning of immunosuppression with the aim of achieving complete discontinuation in 3 months. The primary endpoint is complete immunosuppression discontinuation for 1 year with biochemical and histological stability.

*Results: Six patients initiated LDIL-2 treatment and all achieved sustained >2-fold increase in the absolute number of circulating Tregs after 1 month of treatment (median 4.4, range 2.1-13.3). One patient was found to have sub-clinical rejection while 5 initiated drug withdrawal. Although immunosuppression was discontinued in 2 patients, all patients eventually rejected and required immunosuppression re-institution. Expansion of non-regulatory T and NK cell subsets expressing CD25 was noted in all patients.

*Conclusions: A regimen of 1 million IU daily doses of IL-2 effectively expands circulating Tregs in LT recipients on Tacrolimus but fails to promote the successful discontinuation of immunosuppression. The increases observed in non-Treg circulating immune cell subsets and intra-hepatic lymphocytes indicate lack of selectivity and the need to explore alternative dosing regimens.

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