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

Potential usefulness of Brevibacillus for bacterial cancer therapy: intratumoral provision of... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Gene Therapy Springer Journals

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

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Publisher
Nature Publishing Group US
Copyright
Copyright © 2017 by The Author(s)
Subject
Biomedicine; Biomedicine, general; Gene Therapy; Gene Expression
ISSN
0929-1903
eISSN
1476-5500
D.O.I.
10.1038/s41417-017-0009-7
Publisher site
See Article on Publisher Site

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.

Journal

Cancer Gene TherapySpringer Journals

Published: Dec 18, 2017

References

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