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Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus

Cancer Gene Therapy volume 8, pages 796–802 (2001)Cite this article

Abstract

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors. Cancer Gene Therapy (2001) 8, 796–802

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Authors and Affiliations

  1. Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Ryuya Yamanaka, Susan A Zullo, Jay Ramsey, Masafumi Onodera, Michael Blaese & Kleanthis G Xanthopoulos

  2. Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan

    Ryuya Yamanaka & Ryuichi Tanaka

Authors
  1. Ryuya Yamanaka
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  2. Susan A Zullo
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  3. Jay Ramsey
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  4. Masafumi Onodera
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  5. Ryuichi Tanaka
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  6. Michael Blaese
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  7. Kleanthis G Xanthopoulos
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Correspondence to Ryuya Yamanaka.

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Yamanaka, R., Zullo, S., Ramsey, J. et al. Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus. Cancer Gene Ther 8, 796–802 (2001). https://doi.org/10.1038/sj.cgt.7700367

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