Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats.
Glioma is the most common primary intracranial malignant tumor. Despite advances in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for patients with glioma remains poor. We have explored the effects of using genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in rats. Mesenchymal stem cells isolated from Sprague-Dawley rats can directly suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can also significantly inhibit the growth of glioma and prolong survival in C6 glioma-bearing models. MSCs producing Interleukin-18 infected by adenoviral vector inhibited glioma growth and prolonged the survival of glioma-bearing rats. Transplantation of IL-18 secreting MSCs was associated with enhanced T cell infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma.
Xu
Gang
G
Institute of Neuromedicine, South Medical University, Zhujiang Hospital, Guangzhou, China.
Jiang
Xiao-Dan
XD
Xu
Ying
Y
Zhang
Jing
J
Huang
Fan-Heng
FH
Chen
Zhen-Zhou
ZZ
Zhou
De-Xiang
DX
Shang
Jiang-Hua
JH
Zou
Yu-Xi
YX
Cai
Ying-Qian
YQ
Kou
Sheng-Bin
SB
Chen
Yi-Zhao
YZ
Xu
Ru-Xiang
RX
Zeng
Yan-Jun
YJ
D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D020382:Interleukin-18 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
D020382:Interleukin-18