Monotherapy with the vitamin D analogue MC1288 does not result in prolonged kidney allograft survival in rhesus monkeys

The active form of vitamin D3, 1,25(OH)2D3, has pronounced immunoregulatory properties and is a potential treatment of immune-based disorders. However, the central role of this hormone in calcium and bone metabolism complicates its long-term use as an immunomodulator. Some newly developed vitamin D3-derived analogues, such as MC1288, have an improved immunoregulatory potential and prolong allograft survival in rodent models. Such compounds might be a valuable component of immunosuppressive treatment regimen in transplantation and autoimmunity. The rhesus monkey provides a useful model for the preclinical validation of new therapeutic strategies for transplantation. The present study shows that MC1288 inhibits both proliferation and interferon-gamma production by rhesus peripheral blood mononuclear cells in a mixed lymphocyte reaction. We have tested the maximum tolerated dose of MC1288 in a rhesus monkey model of kidney transplantation. The observed effects on serum calcium and parathyroid hormone confirm the in vivo activity of MC1288. However, as a monotherapy, MC1288 did not cause prolongation of the kidney allograft survival in rhesus monkeys.