Complex cancer gene therapy in mice melanoma.
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.


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.
Dietrich
Arne
A
Clinic for Thoracic, General, and Oncological Surgery, Liebigstrasse 20a, 04103 Leipzig, Germany. dieta@medizin.uni-leipzig.de
Kraus
Katja
K
Brinckmann
Ute
U
Friedrich
Thomas
T
Müller
Anke
A
Liebert
Uwe G
UG
Schönfelder
Manfred
M
D000818:Animals; D018122:B7-1 Antigen / Q000627:therapeutic use; D019470:Biolistics / Q000295:instrumentation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC; D005818:Genetic Engineering / Q000295:instrumentation / Q000379:methods*; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D007371:Interferon-gamma / Q000627:therapeutic use; D018664:Interleukin-12 / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D008546:Melanoma, Experimental / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D012878:Skin Neoplasms / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D018122:B7-1 Antigen; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma