Monotherapy with the vitamin D3 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-γ 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.
Document Type: Research Article
Publication date: May 1, 2006