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Background

KRP203, a structural FTY720 analogue, has 5-fold greater selectivity for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR 1) versus S1PR 3 and 100-fold greater selectivity over S1PR 2 and S1PR 5. Although the immunoregulatory effects of FTY720 have been tested in clinical and experimental research, the therapeutic efficacy of KRP203 in allograft models remains elusive. In this study, we investigated the potential of KRP203 alone and in combination with intragraft injection of CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) to induce islet allograft tolerance.

Methods

BALB/c (H-2 d) mice received transplants of fresh C57BL/10 (H-2 b) islet allografts under the kidney capsule and were treated for 7 days with 0.3, 1.0, or 3.0 mg/kg KRP203 alone or in combination with intragraft-infused Tregs.

Results

Untreated BALB/c mice acutely rejected C57BL/10 islet allografts at a mean survival time of 13 …