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

作者: Jason Koutcher , Ronald Blasberg , Michael Kaplitt , Eli Gilboa , Bernd Gansbacher

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

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