Continuous release of interleukin 12 from microencapsulated engineered cells for colon cancer therapy

World J Gastroenterol. 2003 May;9(5):951-5. doi: 10.3748/wjg.v9.i5.951.


Aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alginates
  • Animals
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Cytokines / blood
  • Cytotoxicity, Immunologic
  • Drug Compounding
  • Gene Expression
  • Genetic Engineering
  • Genetic Therapy / methods*
  • Glucuronic Acid
  • Hexuronic Acids
  • In Vitro Techniques
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Interleukin-12 / therapeutic use
  • Killer Cells, Natural / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection


  • Alginates
  • Cytokines
  • Hexuronic Acids
  • Recombinant Proteins
  • Interleukin-12
  • Glucuronic Acid