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Application of interleukin-2–secreting syngeneic/allogeneic fibroblasts in the treatment of primary and metastatic brain tumors

Cancer Gene Therapy volume 9, pages 464–469 (2002)Cite this article

Abstract

We found previously that mice injected intracerebrally (i.c.) with a mixture of malignant cells and allogeneic fibroblasts genetically engineered to secrete interleukin-2 (IL-2) survived longer than mice in various control groups. The primary goal of this study was to determine if an established i.c. glioma (Gl261) or breast carcinoma (SB-5b) could be treated by injection of IL-2–secreting allogeneic fibroblasts into the tumor region. As an additional objective, these results were compared with the effectiveness of injecting IL-2–secreting allogeneic fibroblasts prior to the introduction of the tumor cells as a means of preventing the development of an i.c. glioma or breast carcinoma. The results demonstrated that treatment of mice bearing an established i.c. glioma or breast carcinoma with IL-2–secreting allogeneic fibroblasts resulted in a prolonged survival. Furthermore, the results demonstrate a significant delay (P<.005) in the development of glioma in the animals treated with either allogeneic nonsecreting or IL-2–secreting fibroblasts prior to introduction of tumor cells. In addition, 50% of the animals pretreated with IL-2–secreting allogeneic fibroblasts injected subsequently with Gl261 glioma cells did not develop a tumor, whereas all of the animals injected with glioma cells alone and 92% of those treated with nonsecreting fibroblasts eventually died. Evidence also exists that long-term immunity was established in the treated animals because there was a significant prolongation of survival in comparison to naïve controls (P<.01) for those animals without evidence of glioma that previously had been immunized with treatment cells when challenged again with tumor cells. In a parallel experiment, 62% of the animals pretreated with nonsecreting allogeneic fibroblasts and 75% of the animals pretreated with allogeneic IL-2–secreting fibroblasts subsequently injected with SB-5b breast carcinoma cells did not develop tumors. The results indicate that IL-2–secreting allogeneic fibroblasts can be effective in the treatment of an established brain tumor. These data also suggest that i.c. injection of allogeneic IL-2–secreting fibroblasts is effective in prevention of the development of a brain tumor when the fibroblasts are introduced into the same site where the tumor is subsequently injected.

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Acknowledgements

We would like to thank Kristin Reepmeyer for technical assistance.

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Authors and Affiliations

  1. Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research, Chicago, IL, USA

    Terry Lichtor, Roberta P Glick, Katherine Tarlock, Shannon Moffett & Elizabeth Mouw

  2. Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA

    Roberta P Glick

  3. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA

    Edward P Cohen

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  1. Terry Lichtor
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  2. Roberta P Glick
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  4. Shannon Moffett
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Correspondence to Terry Lichtor.

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Lichtor, T., Glick, R., Tarlock, K. et al. Application of interleukin-2–secreting syngeneic/allogeneic fibroblasts in the treatment of primary and metastatic brain tumors. Cancer Gene Ther 9, 464–469 (2002). https://doi.org/10.1038/sj.cgt.7700459

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