Particle-mediated cytokine gene therapy leads to antitumor and antimetastatic effects in mouse carcinoma models.
BACKGROUND
We investigated the effects of continuous cancer gene therapy including (antigen-presenting cell) (APC) engineering and local stimulation of the immune system.


METHODS
Lewis lung carcinomas and B16 melanomas, intradermally established on C57/Bl6 mice, were shot using a gene gun every 4th day with a combination of plasmids. The first therapy group received plasmids coding the genes for interleukin (IL)-12 and IL-2. The second therapy group was treated with plasmids coding for B7.1 interferon-gamma (IFN-gamma)/IL-12 alternated by a plasmid coding IL-2. Control were mice without any therapy or treatment with the empty plasmid.


RESULTS
Gene therapy led to reduced tumor sizes in the therapy groups of both models (significant for the Lewis lung carcinoma). We found an enhanced survival and reduced tumor growth rate in the therapy groups; however, the effects were not significant. IL- 12/IL-2 therapy was more effective, compared to B7.1/IFN-gamma/IL-12 and IL-2. Cytokine gene transfer let to a significantly lower metastasis rate in Lewis lung carcinoma.


CONCLUSIONS
Continuous particle-mediated gene transfer is easy to handle and shows good results. Gene therapy combining the genes coding for IL-12 and IL-2 was superior to additional IFN-gamma/B7.1. APC engineering does not appear to be sufficient in these poorly antigenic tumors.
Dietrich
Arne
A
Clinic for Visceral, Thoracic, Vascular and Transplant Surgery, University of Leipzig, Leipzig, Germany. arne.dietrich@medizin.uni-leipzig.de
Becherer
Lars
L
Brinckmann
Ute
U
Hauss
Johann
J
Liebert
Uwe G
UG
Gütz
Anke
A
Aust
Gabriela
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D019470:Biolistics; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics
D016207:Cytokines; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma