BioKnife, a modified sendai virus, to resect malignant tumors

Yoshikazu Yonemitsu, Yasuji Ueda, Mamoru Hasegawa

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationSendai Virus Vector
Subtitle of host publicationAdvantages and Applications
PublisherSpringer Japan
Pages151-169
Number of pages19
ISBN (Electronic)9784431545569
ISBN (Print)4431545557, 9784431545552
DOIs
Publication statusPublished - Sep 1 2013

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)

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    Yonemitsu, Y., Ueda, Y., & Hasegawa, M. (2013). BioKnife, a modified sendai virus, to resect malignant tumors. In Sendai Virus Vector: Advantages and Applications (pp. 151-169). Springer Japan. https://doi.org/10.1007/978-4-431-54556-9_6