Immunoadhesins have been generated in vitro as recombinant protein from human retinal pigment epithelial cells using an E1-deficient adenovirus vector expression system. These immunoadhesins consisted of mouse immune gamma globulin (IgG1) fused to a mouse interleukin-10 (mIL-10) sequence. Previous studies have indicated that an appropriate molecule of 92 kDa was produced with expected activity in vitro. Additionally, a viral interleukin 10- mIgG1 (vIL-10-mIgG1) E1-deleted adenoviral vector has also been produced which is capable of expression of vIL-10-mIgG1 in vivo. Additional E1-deleted vector producing other immunomodulatory cytokines, such as an endogenously active mutant of transforming growth factor beta (TGF-beta1/223,225) has also been produced. In collaboration with McMasters University, this vector is capable of producing significant amount of active TGF-beta1 in vivo. An increase in fibrosis, seen in the lung following pulmonary expression of this molecule, has also been observed in the anterior segment following intracameral injection of the vector. Studies are underway to determine the effect of these immunomodulatory compounds in various rodent models of uveitis.
