BioKnife, a Modified Sendai Virus, to Resect Malignant Tumors

  • Yoshikazu Yonemitsu
  • Yasuji Ueda
  • Mamoru Hasegawa


The M gene-deleted SeV, ΔΜSeV, was found to induce massive cell–cell fusion (syncytia formation) leading to extensive cell death of the entire monolayer culture upon cleavage activation of the viral F glycoprotein on the infected cell surface (see Chap. 3). This finding suggested that ΔΜSeV would have great potential as an oncolytic agent for a solid malignant tumor if it could be further engineered to selectively target the tumor cells. For this targeting we made use of the theory of protease-dependent tissue tropism of SeV (see Chap. 2). Namely, we attempted to render the inactive precursor F0 protein cleavage site of ΔΜSeV susceptible to the proteases overexpressed by diverse tumor cells, including the matrix metalloproteases (MMPs) and urokinase-type plasminogen activator (uPA). In addition, a portion of the cytoplasmic tail of the F protein was deleted to maximize the fusion-inducing capacity. The resultant MMP-targeted and uPA-targeted ΔΜSeVs displayed highly tumor cell-specific killing at the cellular and animal levels. Of these, a uPA-targeted ΔΜSeV appeared to be particularly useful because of its remarkably high efficacy in eradication of tumors in various animal models in addition to its potential diversity of therapeutic targets. We named this virus “BioKnife” because of its desirable nature to resect diverse malignant solid tumors without damaging the surrounding healthy tissues in preclinical studies using animal models. We thus propose a conceptually new strategy in designing an oncolytic virus. Further studies are eagerly awaited to assess its safety and efficacy in clinical settings.


Newcastle Disease Virus Glioblastoma Multiforme Cell Fusion Malignant Pleural Mesothelioma Oncolytic Virus 



We are grateful to M. Inoue at DNAVEC Corporation for his critical reading of the manuscript.


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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Yoshikazu Yonemitsu
    • 1
  • Yasuji Ueda
    • 2
  • Mamoru Hasegawa
    • 2
  1. 1.Faculty of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  2. 2.DNAVEC CorporationIbarakiJapan

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