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Potential usefulness of Brevibacillus for bacterial cancer therapy: intratumoral provision of tumor necrosis factor-α and anticancer effects

Cancer Gene Therapy volume 25, pages 47–57 (2018)Cite this article

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Abstract

Bacterial cancer therapy, wherein bacteria are used as a gene expression system for the exogenous protein of interest in the body, has started becoming a focus area of research; therefore, studying potential bacterial species for use is extremely important. Here, we investigated the use of Brevibacillus choshinensis as an effective and safe provider of anticancer proteins in the body, using a transformant expressing murine tumor necrosis factor-α (mTNF-α). The transformant sustainably provided mTNF-α in tumors in mice for a few hours post-injection. The growth of TNF-α-sensitive tumors was inhibited even by the control transformant, which did not provide mTNF-α; intratumoral mTNF-α provision by Brevibacillus choshinensis had additive effects on tumor growth inhibition. In contrast, intratumorally injected recombinant mTNF-α did not inhibit tumor growth because of rapid elimination from the tumor. Blood biochemical and histochemical analyses showed that intravenous injection of the transformant that did not provide mTNF-α did not lead to tissue injury and dysfunction or infiltration of inflammatory cells over 1 week. Considering the findings, this approach is expected to have a high degree of usability as a delivery system for protein pharmaceuticals, especially from the viewpoints of loading capacity and cost effectiveness.

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Acknowledgements

This work was supported, in part, by JSPS KAKENHI (grant numbers 25640095 and 15K14415). We would like to thank Dr. Hirofumi Hamada (Tokyo University of Pharmacy and Life Sciences, School of Life Sciences) for providing pBluescript SKII+mTNF alpha.

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Authors and Affiliations

  1. Molecular Network Control Imaging Unit, RIKEN Center for Life Science Technologies, Kobe, Japan

    Hidefumi Mukai & Maiko Takahashi

  2. Pathophysiological and Health Science Team, RIKEN Center for Life Science Technologies, Kobe, Japan

    Yasuyoshi Watanabe

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  1. Hidefumi Mukai
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  2. Maiko Takahashi
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  3. Yasuyoshi Watanabe
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Correspondence to Hidefumi Mukai.

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Mukai, H., Takahashi, M. & Watanabe, Y. Potential usefulness of Brevibacillus for bacterial cancer therapy: intratumoral provision of tumor necrosis factor-α and anticancer effects. Cancer Gene Ther 25, 47–57 (2018). https://doi.org/10.1038/s41417-017-0009-7

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