Muscle-targeted interleukin-12 gene therapy of orthotopic hepatocellular carcinoma in mice using in vivo electrosonoporation.
We developed a new potent nonviral gene transfer method into mouse muscles in vivo named "electrosonoporation." We tried in this report to treat murine orthotopic hepatocellular carcinoma (HCC) by muscle-targeted mouse interleukin-12 (mIL-12) gene transfer using in vivo electrosonoporation. I.m. administration of the mIL-12 gene with electrosonoporation elevated serum IL-12 and IFN-gamma and significantly prolonged the survival periods with both growth inhibition of orthotopic HCC and inhibition of spontaneous lung metastasis. The IL-12 gene therapy reduced the number of microvessels and induced more Mac-1-positive cells into HCC. These results show that muscle-targeted mIL-12 gene therapy for orthotopic HCC using in vivo electrosonoporation is very efficient and is thus promising for further clinical trial.
Yamashita
Yo-Ichi
Y
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shimada
Mitsuo
M
Minagawa
Ryosuke
R
Tsujita
Eiji
E
Harimoto
Norifumi
N
Tanaka
Shinji
S
Shirabe
Ken
K
Miyazaki
Jun-Ichi
J
Maehara
Yoshihiko
Y
D000818:Animals; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007273:Injections, Intramuscular / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000378:metabolism; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D016177:Macrophage-1 Antigen; D018664:Interleukin-12