Antitumoral and antimetastatic effects of continuous particle-mediated cytokine gene therapy.
We established a mice tumor model to investigate the effects of continuous cancer gene therapy, including antigen-presenting cell (APC) engineering and local stimulation of the immune system. B16 melanoma or Lewis lung carcinoma cells were injected intradermally on the back of C57/BL6 mice. The overlaying dermis or the tumor was shot with a gene gun (particle-mediated gene transfer) starting 8 days after tumor implantation in the case of the melanoma (Lewis lung carcinoma start day 7), continuing every fourth day thereafter until death. Control groups were mice without any therapy (A) or gene therapy with the empty plasmid (B). Therapy groups (Melanoma) received the genes as follows: group C--day 8, IL-12; day 12, IL-2...; group D--day 8, IFN-gamma/B7.1; day 12, IFN-gamma/B7.1...; group E--day 8, IFN-gamma/B7.1; day 12, IL-12, day 16, IL-2.... Melanoma: Mean survival time was enhanced in all therapy groups significantly, whereby the greatest survival time was found in group C. Tumor growth was reduced in all therapy groups similarly (C and D significant). Lewis Lung: Only mice of group C had an enhanced survival and reduced tumor growth (both significant). An antimetastatic effect was seen in all therapy groups.
Dietrich
Arne
A
Clinic for General Surgery, Surgical Oncology and Thoracic Surgery, Leipzig University, 04103 Leipzig, Germany.
Kraus
Katja
K
Brinckmann
Ute
U
Stockmar
Christoph
C
Müller
Anke
A
Liebert
Uwe Gerd
UG
Schönfelder
Manfred
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000970:Antineoplastic Agents; D016207:Cytokines; D018076:DNA, Complementary