| In recent years gene therapy has evolved as a new treatment, wheregenetically engineered cells can be used to deliver specific substances totarget cells. A novel system for continuous, localized delivery of MIP-3 aprotein to malignant ascites was established. The delivery system wascomposed of MIP-3 a -producing CHO cells encapsulated intoimmuno-isolating sodium alginate. The human CC chemokine, marophageinflammatory protein 3 a (MIP-3 a ), is chemotactic for DCs in vitro. DCsare found at many sites in the body, but mostly at sites of frequent exposureto antigen and where the DC can interact with other components of theimmune system. DC are powerful antigen—presenting cells that function asthe principal activators of T cells and initiate immune responses. Wehypothesized that pcDNA3.1-mediated gene transfer of mMIP-3 a to CHOcells encapsulated into immuno-isolating sodium alginate might induce localaccumulation of DCs and inhibit growth of preexisting malignant ascites. TheCHO cells infected with pcDNA3.1-mMIP-3 a directed expression of mRNAand protein in vitro. Intraperitoneal injection of alginate-encapsulated cellsresulted in local expression of the mMIP-3 a protein and in the localaccumulates of DCs. In syngeneic malignant ascites models, growth ofestablished malignant ascites in mice that received the alginate encapsulated cells treatment was significantly inhibited compared with untreated malignant ascites or malignant ascites injected with match controls. The average volume of ascites fluid, number of tumor cells and leaked RBCs, and the peritoneal microvessel permeability in mice that received the alginate-encapsulated cells treatment were significantly lower than those in the match controls (p<0.001). In summary, our results demonstrated alginate encapsulated producer cells represent a potential delivery system for specific proteins to peritoneal. This strategy may be useful for enlisting DCs to boost anti-tumor immunity against malignant ascites.
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