Generation and optimization of human antagonistic antibodies against TIMP-1 as potential therapeutic agents in fibrotic diseases.

Impaired matrix metalloproteinase 1 (MMP-1) function, as result of the expression of increased levels of tissue inhibitor of metalloproteinase 1 (TIMP-1), plays an important role in the pathopysiolgical mechanism of fibrosis. In a recently performed clinically relevant rat animal model of established liver fibrosis, it could be shown, that blocking the interaction between the metalloproteinase and its inhibitor has beneficial effects in vivo. The rat TIMP-1 specific antagonistic antibody used in this study was derived from a human combinatorial antibody library (HuCAL) and blocks the interaction between rat TIMP-1 and MMP-13, the rat homologue of human MMP-1.