Expression, Purification And Antitumor Activity In Vitro Of Tumor-targeting Fusion Protein RGD-hIL-24

The malignant tumor seriously threaten the health of mankind. The commonly used cancer therapy methods include surgery, radiotherapy and chemotherapy. However, the side effect of radiotherapy and chemotherapy is serious, because normal cells were simultaneously killed. Tumor targeting therapy is a novel method which selectively kills tumor cells by means of specific tumor targeting vehicles, without harming normal cells, and is a central challenge for improving cancer therapies.In the research of tumor targeting therapy, how to select therapy target, tumor-homing vehicles and antitumor element is the most important. Interleukin 24 gene, also called the melanoma differentiation-associated gene 7 (mda-7), is a novel tumor suppressor gene. It was first identified by differentiation induction subtraction hybridization with a human melanoma cell line. Based on its structure, chromosomal location, sequence homology and cytokine-like property, mda-7 has therefore been renamed IL-24 and classified as a member of the expanding IL-10 gene family in 2002. Up to now, a large body of data has demonstrated that administration of IL-24 by means of a replication incompetent adenovirus, Ad.IL-24 , can result in growth suppression and induction of apoptosis in a broad range of cancer cells. In contrast, Ad.IL-24 dose not elicit deleterious effect in normal cells. In addition, IL-24 can activate antitumor immune reaction and suppress the construction of tumor blood vessels. The apparently unique properties of IL-24, particularly its potential as an anticancer gene therapeutic, has made it widely used in cancer gene therapy research. The gene therapy agent Ad.IL-24 (INGN 241) , has gone to PhaseⅡclinical trial. The results demonstrated that this gene is safe and well tolerated by patients.Integrins are a family of cell surface receptors withαandβsubunits. Integrinαvβ3 is expressed on proliferating but not on quiescent endothelial cells. So integrinαvβ3 can be highly expressed on endothelial cells of tumor blood vessels or tumor cells. It is a new target for cancer therapy. The RGD (arginine–glycine–aspartic acid) sequence is known to serve as a recognition moiety between the ligands and integrins. Present data obtained from phage...