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Complex cancer gene therapy in mice melanoma
Arne Dietrich1, Katja Kraus, Ute Brinckmann
1Clinic for Thoracic, General, and Oncological Surgery, Liebigstrasse 20a, 04103 Leipzig, Germany. dieta@medizin.uni-leipzig.de
Objective:
We investigated the effects of continuous cancer gene therapy, including APC engineering and local stimulation of the immune system in a mice melanoma model.
Materials And Methods:
B16 melanoma cells were injected into C57/Bl6 mice intradermally. The overlying dermis or the tumor were shot with different plasmids using a gene gun every 4th day starting 8 days after tumor implantation. Control groups were mice without any therapy or gene therapy as described above with the empty plasmid. Therapy was: group I, IL-12 and IL-2; group II, IFN-gamma/B7.1; group III, IFN-gamma/B7.1, IL-12, and IL-2.
Results:
The median survival time of all therapy groups was significantly enhanced. The longest median survival was in the IL-12/IL-2 group. Tumor growth was reduced in all therapy groups. Control groups suffered a higher rate of metastasis and had fewer inflammatory cells at the tumor site.
Conclusions:
Continuous therapy with the gene gun is easy to handle and shows good results. Therapy with genes for IL-12 and IL-2 was superior to that with additional IFN-gamma/B7.1 or IFN-gamma/B7.1 alone. APC engineering is clearly less sufficient in the case of the B16 melanoma.