Experimental Therapy For Melanoma By Bifidobacterium Infantis-mediated Suicide Gene Transfer Of CD And UPRT

With the advancing of tumor gene therapy, suicide gene therapy has become a highlight in tumor therapy field nowadays. Cytosine Deaminase/5-Fluorocytosine (CD/5-FC) system is one of the most intensely studied gene therapies, and its anti-tumor effect has been experimentally proved . But some disadvantages of this suicide gene system , such as low efficiency of gene transduction, 5-FU resistance in some kind of tumor cells, lack of tumor-targeting gene delivery vectors and so on, are all the important obstacles which greatly restrict its development and clinical application .For tackling these problems , we clone a Uracil Phosphoribosyltransferase (UPRT) gene, which is absent in mammal cells ,into the anaerobicBifidobacterium infantis , combining with the CD/5-FC suicide gene system which has been previously constructed in this Lab, and constructed a novel hypoxia-targeting therapy system with double suicide genes for solid tumor, by using the nonpathogenic anaerobic Bifidobacterium infantis as the vector, which will characteristically colonize in the hypoxic center area of solid tumors. The colonized anaerobic germs can simultaneously express Cytosine Deaminase and Uracil Phosphoribosyltransferase in tumor tissue, which then turn the prodrug 5-FC into the toxic anti-tumor drug. The anti-tumor effects were observed.