Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases.

摘要: We studied the efficacy and tolerance of humanized Ab interfering with signal IL-2 IL-15 receptors in a primate model experimental autoimmune uveoretinitis. The inhibitory effects anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, HuMik beta1, directed at beta-chain shared by IL-15, were tested culture on proliferative response monkey Con A-blast lymphocytes stimulated or IL-15. Uveitis was induced cynomolgus monkeys immunization human recombinant retinal S-antigen. Treatment initiated first sign disease consisted HAT alone combination, vehicle control given i.v. injection twice week for 4 wk. Disease evaluated ocular funduscopy. results showed significant dose-dependent inhibition IL-2-driven proliferation HAT. beta1 ineffective against stimulation, but had marked potentiating effect combination HAT, independent signaling. IL-15-driven inhibited not combination. In monkeys, uveoretinitis evolution significantly treatment. no disease. However, when used two markedly reduced severity inflammation. well tolerated. Only three treated alone, made injected Ab.