A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells.
We studied interleukin (IL)-12 gene therapy using a gene gun as a new autologous vaccination strategy for cancer. In the first experiment, BALB/c mice were inoculated with syngeneic murine renal cancer cells (Renca) intradermally in the abdomen. This was followed by an injection of IL-12 expression plasmid using the gene gun. About 40% of the mice exhibited rejection of the tumor after the treatment and these mice also acquired immunological resistance against a secondary challenge with Renca cells. Based on these results, we examined whether antitumor activity can be potentiated when mice undergo combination treatment with intradermal inoculation of irradiated Renca cells and transfection with IL-12 gene. Inoculation of irradiated Renca cells alone was partially effective in inducing antitumor immunity, whereas the combined treatment remarkably intensified this effect. Moreover, this combined treatment inhibited tumor establishment and enhanced survival of the mice with tumor infiltration by CD4(+) and CD8(+) T cells, even when the treatment was started after tumor-implantation at a distant site. This antitumor effect was antigen specific and we confirmed the induction of antitumor cytotoxic T cells by this treatment. These results show that local cutaneous transfer of IL-12 expression plasmid using gene gun technology enhances systemic and specific antitumor immunity primed by irradiated tumor cells.
Nishitani
Masa-aki
MA
Department of Urology, University of Tokushima School of Medicine, Tokushima, Japan. masaaki@clin.med.tokushima-u.ac.jp
Sakai
Tohru
T
Ishii
Kazunari
K
Zhang
Manxin
M
Nakano
Yoko
Y
Nitta
Yoshio
Y
Miyazaki
Jun-ichi
J
Kanayama
Hiro-omi
HO
Kagawa
Susumu
S
Himeno
Kunisuke
K
D000818:Animals; D019470:Biolistics; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D002455:Cell Division / Q000502:physiology; D003131:Combined Modality Therapy; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D007124:Immunoenzyme Techniques; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D019496:Cancer Vaccines; D017931:DNA Primers; D012333:RNA, Messenger; D018664:Interleukin-12