Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer

We have developed a novel nonviral interleukin 2 (IL-2) gene therapy that d emonstrates significant treatment-specific, antitumor efficacy in combinati on with subtotal surgical resection in a head and neck cancer murine model, Treatment of established head and neck tumors in immunocompetent mice was performed via direct injection with a cationic liposome composed of DOTMA a nd cholesterol formulation carrying DNA plasmid for human IL-2 ( hIL-2) gen e expression, ELISA assays of tumor extracts 24 h after treatment of hIL-2 gene therapy revealed increased local hIL-2 production as well as a formula tion-specific secondary induction of murine IFN-gamma and IL-12. We hypothe size that the paracrine production of multiple cytokines after IL-2 single gene transfer is important for generating a therapeutic effect, and that th is strategy will be well tolerated and effective in combination with surger y for head and neck cancer, In animal experiments where surgery was perform ed in conjunction with an operative site injection of hIL-2 plasmid formula tion, no pre-, intra-, or postoperative toxicity or compromise to wound hea ling was identified. In murine experiments combining partial surgical resec tion with the nonviral gene therapy, significant antitumor efficacy was dem onstrated in the hIL-2 plasmid formulation group compared with empty plasmi d formulation and lactose-injected controls. In a separate experiment using smaller tumor sizes, we also demonstrated that treatment outcomes were dep endent on the technical aspect of the actual treatment injection as well as visualization with surgical access, The hIL-2 plasmid formulation gene the rapy induces local expression of multiple cytokines, results in treatment-s pecific antitumor effects, and circumvents many of the concerns and toxicit y encountered,vith viral gene transfer, These data support the need for con tinued preclinical investigation and the consideration of human clinical tr ials for combination nonviral hIL-2 gene therapy and surgery for head and n eck cancer.