Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 10, October, p. 1135–1143

doi: 10.17219/acem/126298

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Anti-cancer effect of engineered recombinant interleukin 18

Jirakrit Saetang1,A,B,C,D,F, Pennapa Chonpathompikunlert2,B,C, Somporn Sretrirutchai3,B,C, Niran Roongsawang4,A, Kanita Kayasut3,C, Supayang Piyawan Voravuthikunchai5,B, Wanida Sukketsiri6,A, Varomyalin Tipmanee1,A, Surasak Sangkhathat1,7,A,D,E,F

1 Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand

2 Expert Center of Innovative Health Food, Thailand Institute of Scientific and Technological Research, Pathum Thani, Thailand

3 Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand

4 Microbial Cell Factory Research Team, Biorefinery and Bioproduct Technology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand

5 Department of Microbiology and Natural Product Research Center of Excellence, Faculty of Science, Prince of Songkla University, Songkhla, Thailand

6 Department of Pharmacology, Faculty of Science, Prince of Songkla University, Songkhla, Thailand

7 Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand

Abstract

Background. Interleukin 18 (IL-18) is an inflammatory cytokine belonging to the interleukin 1 (IL-1) superfamily, and is known for its role in anti-cancer activity by promoting type 1 immune response, and thus may be applied to cancer immunotherapy. Our previous report has showed 16 times higher activity of engineered E6K+T63A IL-18 than of native IL-18 in vitro. However, no data has been acquired for its anti-cancer effect in animal model.
Objectives. To investigate the anti-cancer effect of engineered E6K+T63A IL-18 as an immune stimulant in vivo.
Material and Methods. Tumor-bearing mice were treated with native IL-18 or E6K or E6K+T63A IL-18 once a day for 10 days after the tumor reached the volume of 100 mm3. Tumor volume and the number of certain immune cell type in the tumor microenvironment were investigated in this study.
Results. The results showed that tumor progression in mice treated with E6K+T63A was slower than in mice treated with E6K and native IL-18. The volume of the tumor was also smaller and the lifespan longer in the E6K+T63A IL-18-treated mice. The proportions of type 1 helper T cell (Th1) and cytotoxic T lymphocyte (CTL) were significantly higher in mice treated with E6K+T63A IL-18.
Conclusion. These results suggest that our engineered IL-18 conferred strong anti-tumor immunity in the animal model.

Key words

Th1, in vivo, interleukin-18, CTL, anti-cancer immunity

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