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

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:mxl19860326
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AIM:To explore the anti-tumor immunity against CT26 colontumor of the microencapsulated cells modified with murineinterleukine-12 (mIL-12) gene.METHODS:Mouse fibroblasts (NIH3T3) were stablytransfected to express mIL-12 using expression plasmidscarrying raiL-12 gene (p35 and p40),and NIH3T3-mIL-12cells were encapsulated in alginate microcapsules for long-term delivery of mIL-12,mIL-12 released from themicroencapsulated NIH3T3-mIL-12 cells was confirmed usingELISA assay.Transplantation of the microencapsulatedNIH3T3-mIL-12 cells was performed in the tumor-bearingmice with CT26 cells.The anti-tumor responses and theanti-tumor activities of the microencapsulated NIH3T3-mIL-12 cells were evaluated.RESULTS:Microencapsulated NIH3T3-mIL-12 cells couldrelease mIL-12 continuously and stably for a long time.Afterthe microencapsulated NIH3T3-mIL-12 cells weretransplanted subcutaneously into the tumor-bearing micefor 21 d,the serum concentrations of mIL-12,mIL-2 andmIFN-γ,the cytotoxicity of the CTL from the splenocytesand the NK activity in the treatment group were significantlyhigher than those in the controls.Moreover,mIL-12 releasedfrom the microencapsulated NIH3T3-mIL-12 cells resultedin a significant inhibition of tumor proliferation and aprolonged survival of tumor-bearing mice.CONCLUSION:The microencapsulated NIH3T3-mIL-12cells have a significant therapeutic effect on the experimentalcolon tumor by activating anti-tumor immune responses invivo.Microencapsulated and genetically engineered cells maybe an extremely versatile tool for tumor gene therapy. AIM: To explore the anti-tumor immunity against CT26 colontumor 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 plasmidscarrying raiL-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 themicroencapsulated 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 theanti-tumor activities of the microencapsulated NIH3T3-mIL-12 cells were all.RESULTS: Microencapsulated NIH3T3-mIL-12 cells couldrelease mIL-12 continuously and stably for a long time. Afterthe 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-γ, the cytotoxicity of the CTL from the splenocytes and the NK activity in the treatment group were significantlyhigher than those in the controls. Moreover, mIL-12 releasedfrom the microencapsulated NIH3T3-mIL-12 cells resulted in a significant inhibition of tumor proliferation and aprolonged survival of the tumor-bearing mice. CONCLUSION : The microencapsulated NIH3T3-mIL-12 cells have a significant therapeutic effect on the experimentalcolon tumor by activating anti-tumor immune responses in HIV. Microencapsulated and genetically engineered cells maybe an extremely versatile tool for tumor gene therapy.
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