RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ Journal Article
| Authors: | Tjuvajev, J.; Gansbacher, B.; Desai, R.; Beattie, B.; Kaplitt, M.; Matei, C.; Koutcher, J.; Gilboa, E.; Blasberg, R. |
| Article Title: | RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-γ |
| 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-y. 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. © 1995, American Association for Cancer Research. All rights reserved. |
| Keywords: | cancer survival; controlled study; cancer growth; nonhuman; comparative study; nuclear magnetic resonance imaging; glioma; brain neoplasms; magnetic resonance imaging; cd8 antigen; animal cell; animal; mice; animal tissue; cell division; interleukin 2; animal experiment; animal model; antineoplastic activity; gene transfer; genetic vectors; transduction, genetic; immune response; gamma interferon; rat; blood-brain barrier; cancer size; gene therapy; brain cancer; rats; cd4 antigen; antibodies, neoplasm; suppressor cell; retroviridae; helper cell; interleukin-2; brain edema; 3t3 cells; gene transfer techniques; interferon type ii; central nervous system diseases; male; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 55 |
| Issue: | 9 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1995-05-01 |
| Start Page: | 1902 |
| End Page: | 1910 |
| Language: | English |
| PUBMED: | 7728757 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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