ISSN:
1432-1335
Keywords:
Interferon
;
Gene therapy
;
Fibroblast
;
Hepatocellular carcinoma
;
Immunotherapy
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The therapeutic effect of the fibroblast-mediated human interferon (IFNα) gene therapy in combination with interleukin-2 (IL-2) activated killer cells (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) on nude mice bearing the human hepatocellular carcinoma (HCC) was investigated. A fibroblast cell clone (NIH3T3-IFNα+) secreting 1024 U/ml human IFNα was obtained from 14 positive clones by BMGNeo-INFα DNA transfection, G418-resistant selection, limiting dilution and assay of IFNα activity. After i.p. implantation of NIH3T3-IFNα+ encapsulated into collagen, serum human IFNα activity could be detected from 12 h to day 15 with a peak at 72 h. AK were prepared from human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated human SMMC 7721 HCC cells. When the NIH3T3-IFNα+ cells were i.p. implanted into the HCC-bearing nude mice, the grown of HCC was inhibited and the survival time of the mice was extended. The growth of HCC was inhibited more obviously when AK was i.v. injected and IL-2 was i.p. injected after the NIH3T3-IFNα+ cells had been implanted. The best therapeutic effect was achieved when NIH3T3-IFNα+ cells were used in combination with IL-2/AK/doxorubicin. All these results suggested that the fibroblast-mediated human IFNα gene therapy could be used to treat the human hepatocellular carcinoma effectively and that when used in combination with IL-2-based adoptive chemoimmunotherapy, the therapeutic effect would be better.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01218361
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