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This thesis examines the use of an antibody and single chain antibody to target myofibroblasts, for the diagnosis and treatment of liver fibrosis. Furthermore the effects of myofibroblasts depletion on inflammation, fibrosis and regeneration are investigated in animal models of chronic and acute liver disease. Liver myofibroblasts have become a focus as a potential therapeutic target as removal or prevention of their activation attenuates liver fibrosis severity. One of the major issues surrounding fibrosis treatment is developing a therapeutic that targets myofibroblasts without causing additional damage to the liver. Using an antibody may provide a solution due to their high specificity for their target antigen. Several antibodies are currently used in the clinic to treat a range of diseases. However no treatment is currently indicated for fibrosis, with transplantation being the only option at the later stages of disease. Our lab has developed a single chain antibody fragment (scab) capable of targeting activated myofibroblasts. Here we examine the use of this antibody as a drug delivery method in vitro and in vivo. This thesis also describes the generation of a human monoclonal IgG to target myofibroblasts and recruit the natural immune effector functions as a safer alternative to toxic drug conjugates. The presence of myofibroblasts is indicative for fibrosis and as such we have used myofibroblasts as a potential imaging target. Using C1-3 conjugated to a fluorophore, we investigated the possibility of grading fibrosis severity, using histological and imaging techniques. |
