RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ

J. Tjuvajev, B. Gansbacher, R. Desai, B. Beattie, M. Kaplitt, C. Matei, J. Koutcher, E. Gilboa, Eli Gilboa

Research output: Contribution to journalArticle

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

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Brain Edema
Glioma
Interferons
Interleukin-2
Growth
Neoplasms
Central Nervous System
Cytokines
Blood-Brain Barrier
Genetic Therapy
Monocytes
Macrophages
Magnetic Resonance Imaging
T-Lymphocytes
Cell Line
Water
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tjuvajev, J., Gansbacher, B., Desai, R., Beattie, B., Kaplitt, M., Matei, C., ... 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.

RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ. / Tjuvajev, J.; Gansbacher, B.; Desai, R.; Beattie, B.; Kaplitt, M.; Matei, C.; Koutcher, J.; Gilboa, E.; Gilboa, Eli.

In: Cancer Research, Vol. 55, No. 9, 01.01.1995, p. 1902-1910.

Research output: Contribution to journalArticle

Tjuvajev, J, Gansbacher, B, Desai, R, Beattie, B, Kaplitt, M, Matei, C, Koutcher, J, Gilboa, E & Gilboa, E 1995, 'RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ', Cancer Research, vol. 55, no. 9, pp. 1902-1910.
Tjuvajev J, Gansbacher B, Desai R, Beattie B, Kaplitt M, Matei C et al. RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ. Cancer Research. 1995 Jan 1;55(9):1902-1910.
Tjuvajev, J. ; Gansbacher, B. ; Desai, R. ; Beattie, B. ; Kaplitt, M. ; Matei, C. ; Koutcher, J. ; Gilboa, E. ; Gilboa, Eli. / RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ. In: Cancer Research. 1995 ; Vol. 55, No. 9. pp. 1902-1910.
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