Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs.
Mesenchymal stem cells (MSCs) were adenovirally engineered to secrete interleukin-12 (AdIL-12-MSCs) and evaluated for their anticarcinogenesis efficacy against three kinds of unestablished tumor models including B16 melanoma, LLC Lewis lung cancer and HCC hepatoma. Injection of AdIL-12-MSCs into protected mice before tumor inoculation prevented all of 12 mice in B16 preventive groups, 10 out of 12 in LLC lung cancer model and 11 out of 12 mice in HCC hepatoma model from developing tumors, whereas the control groups pre-receiving PBS were validated for 100% carcinogenesis; the tumor formation rates in free-AdIL-12 and vacant MSC groups were unveiled between approximately 83 and 100% even with plentiful angiogenesis and newborn lymphatic vessels, as well as distant metastases. As a novel approach, AdIL-12-MSC has revealed expected preventive effects on carcinogenesis (P<0.01) with low-toxic, broad-spectrum and long-range superiorities. In conclusion, our data indicate that AdIL-12-MSC possess the potential for tropism to preclinical tumor lesions and deprives surviving or hibernating tumor cells, which have escaped from conventional treatments, of revival and recurrence.
Chen
Xian-cheng
XC
National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China Medical School, Sichuan University, People's Republic of China.
Wang
Rui
R
Zhao
Xia
X
Wei
Yu-quan
YQ
Hu
Min
M
Wang
Yang-sheng
YS
Zhang
Xiao-wei
XW
Zhang
Ru
R
Zhang
Lin
L
Yao
Bin
B
Wang
Lian
L
Jia
Yong-qian
YQ
Zeng
Ting-ting
TT
Yang
Jin-liang
JL
Tian
Ling
L
Kan
Bing
B
Lin
Xiao-juan
XJ
Lei
Song
S
Deng
Hong-xin
HX
Wen
Yan-jun
YJ
Mao
Yong-qiu
YQ
Li
Jiong
J
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D045744:Cell Line, Tumor; D005818:Genetic Engineering; D018664:Interleukin-12 / Q000235:genetics*; D008113:Liver Neoplasms / Q000517:prevention & control; D008175:Lung Neoplasms / Q000517:prevention & control; D008546:Melanoma, Experimental / Q000517:prevention & control; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice
D018664:Interleukin-12