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Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model

Cancer Gene Therapy volume 9, pages 44–52 (2002)Cite this article

Abstract

The combined therapeutic effect of cytokine-producing cancer cell vaccines and local radiotherapy was studied in a mouse glioma 261 (Gl261) brain tumor model. Brain tumor–bearing mice were treated with cytokine (IL-4, IL-6, IL-7, GM-CSF, TNF-α, LIF, LT) producing vaccines made by in vitro transduction of Gl261 cells with the corresponding adenoviral vectors. Vaccines producing either IL-4 or GM-CSF cured 20–40% of mice. The antitumor effect strongly depended on the secreted cytokine level. Vaccination therapy induced specific activation of cytotoxic T lymphocytes measured by cell-mediated cytotoxicity assay. Brain tumors were heavily infiltrated by CD4+ lymphocytes after treatment with IL-4– or GM-CSF–secreting cells. GM-CSF vaccination induced moderate CD8+ infiltration, as well. Depleting either CD4+ or CD8+ lymphocyte subsets abolished the anticancer effect of GM-CSF–expressing cells. Strong synergism was observed by combining cytokine vaccination (GM-CSF, IL-4, IL-12) with local tumor irradiation: about 80–100% of the glioma-bearing mice was cured. The high efficiency of combined treatment was maintained even under suboptimal conditions when neither of the modalities cured any of the mice alone. This suggests that vaccination therapy might open a new potential in the clinical treatment of high-grade gliomas when applied as adjuvant to existing treatment modalities.

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Acknowledgements

This work was supported by an international collaborative ICGEB (CRP/HUN98-02-t2) Grant and Hungarian National Founds: ETT 6100/1/2000, ETT 247/1996, OTKA T-025810, OTKA T-032499, OMFB 96-97-65-1201 to GS, and OTKA T-025333, AKP-96/2-654-3.2 to EH. The authors thank Maria Frigyesi and Erzsebet Fekete for technical assistance.

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Authors and Affiliations

  1. Department of Molecular and Tumor Radiobiology, National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary

    Katalin Lumniczky, Szilvia Desaknai, Egon J Hidvegi & Geza Safrany

  2. Department of Radiation Therapy, National Institute for Oncology, Budapest, Hungary

    Laszlo Mangel

  3. First Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Bela Szende

  4. Department of Molecular Medicine, Biomedical Research Center, Sapporo Medical University, Sapporo, Japan

    Hirofumi Hamada

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  1. Katalin Lumniczky
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Correspondence to Geza Safrany.

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Lumniczky, K., Desaknai, S., Mangel, L. et al. Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model. Cancer Gene Ther 9, 44–52 (2002). https://doi.org/10.1038/sj.cgt.7700398

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