RG-2 Glioma Growth Attenuation and Severe Brain Edema Caused By Local Production of Interleukin-2 and Interferon-γ

Juri Tjuvajev, Revathi Desai, Bradley Beattie, Michael Kaplitt, Ronald Blasberg, Cornelia Matei, Jason Koutcher, Bernd Gansbacher, Eli Gilboa

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-γ within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-γ generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell- mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-γ. Central nervous system toxicity included blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-γ gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.

Original languageEnglish (US)
Pages (from-to)1902-1910
Number of pages9
JournalCancer Research
Volume55
Issue number9
StatePublished - May 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tjuvajev, J., Desai, R., Beattie, B., Kaplitt, M., Blasberg, R., Matei, C., Koutcher, J., Gansbacher, B., & Gilboa, E. (1995). RG-2 Glioma Growth Attenuation and Severe Brain Edema Caused By Local Production of Interleukin-2 and Interferon-γ. Cancer Research, 55(9), 1902-1910.