title: Monotherapy with the vitamin D analogue MC1288 does not result in prolonged kidney allograft survival in rhesus monkeys.
abstract: 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.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. vierboom@bprc.nl
authors.forename: Michel
authors.initials: M
authors.lastname: Vierboom
authors.forename: C
authors.initials: C
authors.lastname: Johnsson
authors.forename: Bert
authors.initials: B
authors.lastname: 't Hart
authors.forename: Margreet
authors.initials: M
authors.lastname: Jonker
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000379:methods*; D008214:Lymphocytes / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D020714:Maximum Tolerated Dose; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives*
chemical_list: D002120:Calcium Channel Agonists; D007166:Immunosuppressive Agents; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium