Several agents that inhibit IL-15 activity have been developed, including soluble IL-15Rα, mutant IL-15 molecules, and antibodies specific for IL-2/IL-15Rβ. For example, in vivo, the IL-15 mutant markedly diminished antigen-specific delayed-type hypersensitivity responses in Balb/c mice and increased survival of pancreatic islet cell allografts. The use of soluble high-affinity IL-15Rα inhibited the development of mouse collagen-induced arthritis and inhibited allograft rejection. An antibody specific for IL-15 has been efficacious in mouse models of psoriasis. This antibody is now in a phase I/II clinical trial in patients with rheumathoid arthritis. Finally, a humanized antibody specific for IL-2/IL-15Rβ when administered as a single agent prolonged cardiac-allograft survival in cynomolgus monkeys, and only minimal toxicity was noted when this antibody was given in a phase I trial to patients with T cell large granular lymphocytic leukemia.
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