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October 2014 Volume 45 Issue 4

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A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model

  • Authors:
    • Kosuke Higashi
    • Shoichi Hazama
    • Atsuhiro Araki
    • Kiyoshi Yoshimura
    • Norio Iizuka
    • Shigefumi Yoshino
    • Takafumi Noma
    • Masaaki Oka
  • View Affiliations / Copyright

    Affiliations: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan
    Copyright: © Higashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1412-1420
    |
    Published online on: July 22, 2014
       https://doi.org/10.3892/ijo.2014.2557
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Abstract

A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination.
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1 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Marin JJ, Sanchez de Medina F, Castano B, Bujanda L, Romero MR, Martinez-Augustin O, Moral-Avila RD and Briz O: Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer. Drug Metab Rev. 44:148–172. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F and de Gramont A: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 27:3109–3116. 2009. View Article : Google Scholar

4 

Okamura H, Tsutsi H, Komatsu T, et al: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 378:88–91. 1995. View Article : Google Scholar : PubMed/NCBI

5 

Sugie T, Murata-Hirai K, Iwasaki M, Morita CT, Li W, Okamura H, Minato N, Toi M and Tanaka Y: Zoledronic acid-induced expansion of gammadelta T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells. Cancer Immunol Immunother. 62:677–687. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Dao T, Ohashi K, Kayano T, Kurimoto M and Okamura H: Interferon-gamma inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell Immunol. 173:230–235. 1996. View Article : Google Scholar : PubMed/NCBI

7 

Tsutsui H, Nakanishi K, Matsui K, Higashino K, Okamura H, Miyazawa Y and Kaneda K: IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol. 157:3967–3973. 1996.PubMed/NCBI

8 

Kohyama M, Saijyo K, Hayasida M, Yasugi T, Kurimoto M and Ohno T: Direct activation of human CD8+cytotoxic T lymphocytes by interleukin-18. Jpn J Cancer Res. 89:1041–1046. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Yoshimura K, Hazama S, Iizuka N, Yoshino S, Yamamoto K, Muraguchi M, Ohmoto Y, Noma T and Oka M: Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence. Cancer Gene Ther. 8:9–16. 2001. View Article : Google Scholar

10 

Choi IK, Lee JS, Zhang SN, Park J, Sonn CH, Lee KM and Yun CO: Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rbeta2 or IL-18Ralpha. Gene Ther. 18:898–909. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Wirth T, Parker N and Yla-Herttuala S: History of gene therapy. Gene. 525:162–169. 2013. View Article : Google Scholar

12 

Beltinger C, Fulda S, Kammertoens T, Meyer E, Uckert W and Debatin KM: Herpes simplex virus thymidine kinase/ganciclovir-induced apoptosis involves ligand-independent death receptor aggregation and activation of caspases. Proc Natl Acad Sci USA. 96:8699–8704. 1999. View Article : Google Scholar

13 

Ladjemi MZ, Jacot W, Chardes T, Pelegrin A and Navarro-Teulon I: Anti-HER2 vaccines: new prospects for breast cancer therapy. Cancer Immunol Immunother. 59:1295–1312. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Chen SH, Kosai K, Xu B, Pham-Nguyen K, Contant C, Finegold MJ and Woo SL: Combination suicide and cytokine gene therapy for hepatic metastases of colon carcinoma: sustained antitumor immunity prolongs animal survival. Cancer Res. 56:3758–3762. 1996.PubMed/NCBI

15 

Zhang JH, Wan MX, Yuan JY and Pan BR: Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901. World J Gastroenterol. 10:26–30. 2004.

16 

Xu Y, Hou J, Liu Z, Yu H, Sun W, Xiong J, Liao Z, Zhou F, Xie C and Zhou Y: Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma. J Transl Med. 9:392011. View Article : Google Scholar : PubMed/NCBI

17 

Hall SJ, Canfield SE, Yan Y, Hassen W, Selleck WA and Chen SH: A novel bystander effect involving tumor cell-derived Fas and FasL interactions following Ad.HSV-tk and Ad.mIL-12 gene therapies in experimental prostate cancer. Gene Ther. 9:511–517. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Tsutsui H, Matsui K, Kawada N, Hyodo Y, Hayashi N, Okamura H, Higashino K and Nakanishi K: IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol. 159:3961–3967. 1997.PubMed/NCBI

19 

Wirth T, Kuhnel F and Kubicka S: Telomerase-dependent gene therapy. Curr Mol Med. 5:243–251. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Hara T, Noma T, Yamashiro Y, Naito K and Nakazawa A: Quantitative analysis of telomerase activity and telomerase reverse transcriptase expression in renal cell carcinoma. Urol Res. 29:1–6. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Hazama S, Noma T, Wang F, Iizuka N, Ogura Y, Yoshimura K, Inoguchi E, Hakozaki M, Hirose K, Suzuki T and Oka M: Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo. Br J Cancer. 80:1420–1426. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Oka M, Iizuka N, Yamamoto K, et al: The influence of interleukin- 6 on the growth of human esophageal cancer cell lines. J Interferon Cytokine Res. 16:1001–1006. 1996.PubMed/NCBI

23 

Toshimitsu H, Iizuka N, Yamamoto K, Kawauchi S, Oga A, Furuya T, Oka M and Sasaki K: Molecular features linked to the growth-inhibitory effects of gemcitabine on human pancreatic cancer cells. Oncol Rep. 16:1285–1291. 2006.PubMed/NCBI

24 

Corbett TH, Griswold DP Jr, Roberts BJ, Peckham JC and Schabel FM Jr: Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 35:2434–2439. 1975.PubMed/NCBI

25 

Araki A, Hazama S, Yoshimura K, Yoshino S, Iizuka N and Oka M: Tumor secreting high levels of IL-15 induces specific immunity to low immunogenic colon adenocarcinoma via CD8+T cells. Int J Mol Med. 14:571–576. 2004.PubMed/NCBI

26 

Correale P, Cusi MG, Del Vecchio MT, et al: Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro. J Immunol. 175:820–828. 2005.

27 

Ji Q, Castelli L and Goverman JM: MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8(+) T cells. Nat Immunol. 14:254–261. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Wahl LM and Kleinman HK: Tumor-associated macrophages as targets for cancer therapy. J Natl Cancer Inst. 90:1583–1584. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G and Lee WM: Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest. 101:1441–1452. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Ochs K and Kaina B: Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res. 60:5815–5824. 2000.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Higashi K, Hazama S, Araki A, Yoshimura K, Iizuka N, Yoshino S, Noma T and Oka M: A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model. Int J Oncol 45: 1412-1420, 2014.
APA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S. ... Oka, M. (2014). A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model. International Journal of Oncology, 45, 1412-1420. https://doi.org/10.3892/ijo.2014.2557
MLA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45.4 (2014): 1412-1420.
Chicago
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45, no. 4 (2014): 1412-1420. https://doi.org/10.3892/ijo.2014.2557
Copy and paste a formatted citation
x
Spandidos Publications style
Higashi K, Hazama S, Araki A, Yoshimura K, Iizuka N, Yoshino S, Noma T and Oka M: A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model. Int J Oncol 45: 1412-1420, 2014.
APA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S. ... Oka, M. (2014). A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model. International Journal of Oncology, 45, 1412-1420. https://doi.org/10.3892/ijo.2014.2557
MLA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45.4 (2014): 1412-1420.
Chicago
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45, no. 4 (2014): 1412-1420. https://doi.org/10.3892/ijo.2014.2557
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