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Induction of immune response by IL-6 gene-modified leukemia cells

  • Gene Therapy
  • Published:
Chinese Journal of Cancer Research

Abstract

Human IL-6 gene was transduced into FBL-3 murine erythroleukemia cellsin vitro by calcium phosphate co-participation. After selection in the presence of G418, limiting dilution and biological activity assay, G418 resistant clone that secreted the highest level of IL-6 (225.6 U/ml) was selected out of 24 IL-6-secreting clones. The FBL-3 cells secreting the highest level of IL-6 (FBL-3-IL-6) showed decreased growth potential and clonogenicityin vitro. Inhibition of cell growth and clone formation was found to be closely related to the level of IL-6 secretion. FBL-3-IL-6 cells grew more slowly than wild-type FBL-3 leukemia cells and FBL-3 cells secreting lower level of IL-6 (21.3 U/ml) when inoculated s.c. into C57BL/6 mice. The mice inoculated with FBL-3-IL-6 cells showed prolonged survival period than those inoculated with control leukemia cells. Increased cytotoxic activities of splenic NK and CTL were found in mice inoculated with FBL-3-IL-6 cells. The secretions of IL-2, TNF and GM-CSF from murine splenocytes were also found to be greatly elevated after the inoculation of FBL-3-IL-6 leukemia cells. These data suggested that transduction of IL-6 gene into FBL-3 cells magnificently decreased the tumorigenicity and increased the immunogenicity of the leukemia cells, could induce specific and nonspecific antitumor immune responses. IL-6 gene-modified leukemia cells might be of great interests to be used as vaccine for the treatment of leukemia.

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References

  1. Anderson WF. Gene therapy for cancer. Hum Gene Ther 1994; 5:1.

    Article  PubMed  Google Scholar 

  2. Colombo MP, Forni G. Cytokine gene transfer into tumor inhibition and tumor therapy: where are we now? Immunol Today 1994; 15: 48.

    Article  PubMed  CAS  Google Scholar 

  3. Muller JJ, Mclntosh Jk, Jablons DM, et al. Antitumor activity of recombinant interleukin-6 in mice. J Exp Med 1990; 171: 629.

    Article  Google Scholar 

  4. Gallahger G, Stimson WH, Findlay J, et al. Interleukin 6 enhances the induction of human lymphokine activated killer cells. Cancer Immunol Immunother 1990; 31:49.

    Article  Google Scholar 

  5. Givon T, Slavin S, Haran-Ghera N, et al. Antitumor effects of human recombinant interleukin 6 on acute myloid leukemia in mice and in cell cultures. Blood 1992; 79:2392.

    PubMed  CAS  Google Scholar 

  6. Nebber J, Rosenberg SA. Phase I studies of the pharmacokinetic, toxicities and biological effects of interleukin-6 in patients with refractory advanced malignancies. J Immunother 1993; 13:74.

    Google Scholar 

  7. 1994; 10(5): 289.

  8. Sun WH, Kreisle RA, Phillips AW, et al.In vivo and in vitro characteristics of interleukin-6-transfected B16 melanoma cells. Cancer Res 1992; 52:5412.

    PubMed  CAS  Google Scholar 

  9. Porgador A, Tzehoval E, Katz A, et al. Interleukin-6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutics competence against parental metastatic cells. Cancer Res, 1992;52:3679–3686

    PubMed  CAS  Google Scholar 

  10. Ohe Y, Podack ER, Olsen KJ, et al. Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumor growth rate but cause weight loss and shorten survival in syngenic mice. Br J Cancer 1993;67:939–944

    PubMed  CAS  Google Scholar 

  11. Mullen CA, Coale MM, Levy AT, et al. Fibrosarcoma cells transduced with IL-6 gent exhibit reduced tumorigenicity, increased immunogenicity and decreased metastatic potential. Cancer Res 1992; 52: 6020.

    PubMed  CAS  Google Scholar 

  12. Dougherty GJ, Thacker JD, Lavey RS, et al. Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growthin vivo. Cancer Immunol Immunother 1994; 38:339.

    Article  PubMed  CAS  Google Scholar 

  13. Cao X, Zhang W, Gu S, et al. Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2. J Cancer Res Clin Oncol 1996; 121:721.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, Second Military Medical University, 200433, Shanghai

    Cao Xuetao, Ge Lingfu, Ju DianWen, Yu Yizhi, Tao Qun & Zhang Weiping

Authors
  1. Cao Xuetao
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  2. Ge Lingfu
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  3. Ju DianWen
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  4. Yu Yizhi
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  5. Tao Qun
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  6. Zhang Weiping
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Additional information

This work was supported by a grant from the National Natural Science Foundation of China (No.39730420).

This is one of papers of the special issue on gene therapy research (Chin J Cancer Res Vol. 9 No. 4 December, 1997).

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Cao, X., Ge, L., Ju, D. et al. Induction of immune response by IL-6 gene-modified leukemia cells. Chin J Cancer Res 10, 9–15 (1998). https://doi.org/10.1007/BF02974652

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  • DOI: https://doi.org/10.1007/BF02974652

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