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Pharmaceutics 2015, 7(3), 165-174; doi:10.3390/pharmaceutics7030165

Novel Antitumor Strategy Utilizing a Plasmid Expressing a Mycobacterium tuberculosis Antigen as a “Danger Signal” to Block Immune Escape of Tumor Cells

1
Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo 189-0021, Japan
2
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan
3
Department of Home Economics, Otsuma Women's University, 12 Sanbancho, Chiyoda-ku, Tokyo 102-8357, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Keiji Itaka
Received: 31 May 2015 / Revised: 4 July 2015 / Accepted: 15 July 2015 / Published: 24 July 2015
(This article belongs to the Special Issue New Paradigm of Gene Therapy)
View Full-Text   |   Download PDF [1847 KB, uploaded 27 July 2015]   |  

Abstract

Immune escape of tumor cells is one of the main obstacles hindering the effectiveness of cancer immunotherapy. We developed a novel strategy to block immune escape by transfecting tumor cells in vivo with genes of pathogenic antigens from Mycobacterium tuberculosis (TB). This induces presentation of the TB antigen on tumor cell surfaces, which can be recognized by antigen presenting cells (APCs) as a “danger signal” to stimulate antitumor immune response. This strategy is also expected to amplify the immune response against tumor-associated antigens, and block immune escape of the tumor. DNA/PEI/chondroitin sulfate ternary complex is a highly effective non-viral gene vector system for in vivo transfection. A therapeutic complex was prepared using a plasmid encoding the TB antigen, early secretory antigenic target-6 (ESAT-6). This was injected intratumorally into syngeneic tumor-bearing mice, and induced significant tumor growth suppression comparable to or higher than similar complexes expressing cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12). Co-transfection of the cytokine-genes and the ESAT-6-gene enhanced the antitumor efficacy of either treatment alone. In addition, complete tumor regression was achieved with the combination of ESAT-6 and IL-2 genes. View Full-Text
Keywords: early secretory antigenic target-6; immuno-gene therapy; non-viral; transfection; plasmid; danger signal; cytokine; Mycobacterium tuberculosis; immune escape; nanoparticle early secretory antigenic target-6; immuno-gene therapy; non-viral; transfection; plasmid; danger signal; cytokine; Mycobacterium tuberculosis; immune escape; nanoparticle
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Koyama, Y.; Yoshihara, C.; Ito, T. Novel Antitumor Strategy Utilizing a Plasmid Expressing a Mycobacterium tuberculosis Antigen as a “Danger Signal” to Block Immune Escape of Tumor Cells. Pharmaceutics 2015, 7, 165-174.

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