Continuous release of interleukin 12 from microencapsulated engineered cells for colon cancer therapy.
OBJECTIVE
To explore the anti-tumor immunity against CT26 colon tumor of the microencapsulated cells modified with murine interleukine-12 (mIL-12) gene.


METHODS
Mouse fibroblasts (NIH3T3) were stably transfected to express mIL-12 using expression plasmids carrying mIL-12 gene (p35 and p40), and NIH3T3-mIL-12 cells were encapsulated in alginate microcapsules for long-term delivery of mIL-12. mIL-12 released from the microencapsulated NIH3T3-mIL-12 cells was confirmed using ELISA assay. Transplantation of the microencapsulated NIH3T3-mIL-12 cells was performed in the tumor-bearing mice with CT26 cells. The anti-tumor responses and the anti-tumor activities of the microencapsulated NIH3T3-mIL-12 cells were evaluated.


RESULTS
Microencapsulated NIH3T3-mIL-12 cells could release mIL-12 continuously and stably for a long time. After the microencapsulated NIH3T3-mIL-12 cells were transplanted subcutaneously into the tumor-bearing mice for 21 d, the serum concentrations of mIL-12, mIL-2 and mIFN-gamma, the cytotoxicity of the CTL from the splenocytes and the NK activity in the treatment group were significantly higher than those in the controls. Moreover, mIL-12 released from the microencapsulated NIH3T3-mIL-12 cells resulted in a significant inhibition of tumor proliferation and a prolonged survival of tumor-bearing mice.


CONCLUSIONS
The microencapsulated NIH3T3-mIL-12 cells have a significant therapeutic effect on the experimental colon tumor by activating anti-tumor immune responses in vivo. Microencapsulated and genetically engineered cells may be an extremely versatile tool for tumor gene therapy.
Zheng
Shu
S
Cancer Institute, Zhejiang University, Hangzhou 310009, Zhejiang Province, China. zhengshu@zju.edu.cn
Xiao
Zuo-Xiang
ZX
Pan
Yue-Long
YL
Han
Ming-Yong
MY
Dong
Qi
Q
D016475:3T3 Cells; D000464:Alginates; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D004339:Drug Compounding; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000464:Alginates; D016207:Cytokines; D006603:Hexuronic Acids; D011994:Recombinant Proteins; D018664:Interleukin-12; D020723:Glucuronic Acid