Systemic p53 gene therapy in combination with radiation results in human tumor regression

A long-standing goal in gene therapy for cancer is a systemic delivery syst em that selectively targets tumor cells including metastases. We optimized a folate containing cationic liposome system for the systemic delivery of w tp53 to squamous cell carcinoma of the head and neck. The folate ligand, wh ich serves to target the complier to tumor cells, increased the transfectio n efficiency by facilitating transient gene transfection. This system was d emonstrated to be exceedingly tumor-selective in that normal tissues, inclu ding the highly proliferative gut and bone marrow, were not transfected. Th e systemic delivery by this method of wild-type p53 to established mouse xe nografts markedly sensitized these human tumors to radiotherapy. This combi nation of systemic p53 gene therapy and conventional radiotherapy resulted in complete tumor regression and inhibition of their recurrence long-term, Similar results were also demonstrated with another model system, prostate cancer cell line DU145, This addition of a molecular component could provid e an improved therapeutic approach for cancers of the head and neck and oth er forms of cancer as well.