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Article

Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death

  • Authors:
    • Giou-Teng Yiang
    • Ruey-Hwang Chou
    • Wei-Jung Chang
    • Chyou-Wei Wei
    • Yung-Luen Yu
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Medicine, Tzu Chi University, Hualien 970, Taiwan, R.O.C, Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C, Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Shalu, Taichung 433, Taiwan, R.O.C
  • Pages: 321-325
    |
    Published online on: January 7, 2013
       https://doi.org/10.3892/mco.2013.60
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Abstract

Glioblastoma is the most aggressive primary brain tumor and its prognosis remains poor despite different treatment modalities including surgery, radiotherapy and chemotherapy. Therefore, more useful treatments for glioblastoma patients are required. Human interleukin 15 (hIL15) is an immunomodulator that has antitumor activities. hIL15 combined with gene therapy method is also currently under cosideration as a treatment option. Since recombinant adenoassociated virus serotype 2 (rAAV2) with low immunogenicity and long-term gene expression in human clinical trials has been demonstrated, rAAV2 encoding hIL15 (rAAV2‑hIL15) were used to inhibit human glioblastoma growth in the present study. rAAV2-hIL15, which is able to express IL15 protein with bioactivity, was successfully produced and purified. Data of this study demonstrated that the long-term expression of rAAV2‑hIL15 enhances immunoglobulin (Ig) production and the cytotoxic activity of lymphokine-activated killer (LAK) cells. In addition, results of the present study showed that rAAV2‑hIL15 delays tumor growth on a xenografted human glioblastoma mice model. Taken together, these results indicated that rAAV2‑hIL15 constitutes a powerful and potent gene immunotherapy method for human glioblastoma treatment.
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1 

Daneyemez M, Gezen F, Canakci Z and Kahraman S: Radical surgery and reoperation in supratentorial malignant glial tumors. Minim Invasive Neurosurg. 41:209–213. 1998. View Article : Google Scholar : PubMed/NCBI

2 

Stephenson KB, Barra NG, Davies E, Ashkar AA and Lichty BD: Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity. Cancer Gene Ther. 19:238–246. 2012. View Article : Google Scholar

3 

McBride WH: Integration of adenovirus thymidine kinase suicide-gene therapy with surgery and radiation therapy for malignant glioma. Future Oncol. 8:17–20. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Srivastava D, Joshi G, Somasundaram K and Mulherkar R: Mode of cell death associated with adenovirus-mediated suicide gene therapy in HNSCC tumor model. Anticancer Res. 31:3851–3857. 2011.PubMed/NCBI

5 

Munger W, DeJoy SQ, Jeyaseelan R Sr, et al: Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. Cell Immunol. 165:289–293. 1995. View Article : Google Scholar : PubMed/NCBI

6 

Carson WE, Giri JG, Lindemann MJ, et al: Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med. 180:1395–1403. 1994. View Article : Google Scholar : PubMed/NCBI

7 

Mrozek E, Anderson P and Caligiuri MA: Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood. 87:2632–2640. 1996.PubMed/NCBI

8 

Sparano JA, Fisher RI, Weiss GR, et al: Phase II trials of high-dose interleukin-2 and lymphokine-activated killer cells in advanced breast carcinoma and carcinoma of the lung, ovary, and pancreas and other tumors. J Immunother Emphasis Tumor Immunol. 16:216–223. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Chapoval AI, Fuller JA, Kremlev SG, Kamdar SJ and Evans R: Combination chemotherapy and IL15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells. J Immunol. 161:6977–6984. 1998.PubMed/NCBI

10 

Lasek W, Basak G, Switaj T, et al: Complete tumour regressions induced by vaccination with IL-12 gene-transduced tumour cells in combination with IL15 in a melanoma model in mice. Cancer Immunol Immunother. 53:363–372. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Rubinstein MP, Kadima AN, Salem ML, Nguyen CL, Gillanders WE and Cole DJ: Systemic administration of IL15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells. J Immunol. 169:4928–4935. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Croce M, Meazza R, Orengo AM, et al: Sequential immunogene therapy with interleukin-12- and interleukin-15-engineered neuroblastoma cells cures metastatic disease in syngeneic mice. Clin Cancer Res. 11:735–742. 2005.PubMed/NCBI

13 

Suzuki K, Nakazato H, Matsui H, et al: NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer. J Leukoc Biol. 69:531–537. 2001.PubMed/NCBI

14 

Kimura K, Nishimura H, Hirose K, Matsuguchi T, Nimura Y and Yoshikai Y: Immunogene therapy of murine fibrosarcoma using IL15 gene with high translation efficiency. Eur J Immunol. 29:1532–1542. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Ponnazhagan S, Curiel DT, Shaw DR, Alvarez RD and Siegal GP: Adeno-associated virus for cancer gene therapy. Cancer Res. 61:6313–6321. 2001.PubMed/NCBI

16 

Xiao X, Li J and Samulski RJ: Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol. 70:8098–8108. 1996.PubMed/NCBI

17 

Jennings K, Miyamae T, Traister R, et al: Proteasome inhibition enhances AAV-mediated transgene expression in human synoviocytes in vitro and in vivo. Mol Ther. 11:600–607. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Jooss K, Yang Y, Fisher KJ and Wilson JM: Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers. J Virol. 72:4212–4223. 1998.PubMed/NCBI

19 

Emborg ME, Carbon M, Holden JE, et al: Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. J Cereb Blood Flow Metab. 27:501–509. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kaplitt MG, Feigin A, Tang C, et al: Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet. 369:2097–2105. 2007.PubMed/NCBI

21 

Yu YL, Wei CW, Chen YL, Chen MH and Yiang GT: Immunotherapy of breast cancer by single delivery with rAAV2-mediated interleukin-15 expression. Int J Oncol. 36:365–370. 2010.PubMed/NCBI

22 

Yiang GT, Chou PL, Tsai HF, et al: Immunotherapy for SV40 T/t antigen-induced breast cancer by recombinant adeno-associated virus serotype 2 carrying interleukin-15 in mice. Int J Mol Med. 29:809–814. 2012.PubMed/NCBI

23 

Yiang GT, Harn HJ, Yu YL, et al: Immunotherapy: rAAV2 expressing interleukin-15 inhibits HeLa cell tumor growth in mice. J Biomed Sci. 16:472009. View Article : Google Scholar : PubMed/NCBI

24 

Kayama T, Kumabe T, Tominaga T and Yoshimoto T: Prognostic value of complete response after the initial treatment for malignant astrocytoma. Neurol Res. 18:321–324. 1996.PubMed/NCBI

25 

Kowalczuk A, Macdonald RL, Amidei C, et al: Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas. Neurosurgery. 41:1028–1038. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Li YM and Hall WA: Targeted toxins in brain tumor therapy. Toxins (Basel). 2:2645–2662. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Ahmed AU, Ulasov IV, Mercer RW and Lesniak MS: Maintaining and loading neural stem cells for delivery of oncolytic adenovirus to brain tumors. Methods Mol Biol. 797:97–109. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Kim CY, Park SH, Jeong M, et al: Preclinical studies for pharmacokinetics and biodistribution of Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy. Exp Mol Med. 43:580–586. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Lee EX, Lam DH, Wu C, et al: Glioma gene therapy using induced pluripotent stem cell derived neural stem cells. Mol Pharm. 8:1515–1524. 2011. View Article : Google Scholar : PubMed/NCBI

30 

King GD, Muhammad AK, Larocque D, et al: Combined Flt3L/TK gene therapy induces immunological surveillance which mediates an immune response against a surrogate brain tumor neoantigen. Mol Ther. 19:1793–1801. 2011. View Article : Google Scholar

31 

Heilbronn R and Weger S: Viral vectors for gene transfer: current status of gene therapeutics. Handb Exp Pharmacol. 143–170. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Lundstrom K: Gene therapy applications of viral vectors. Technol Cancer Res Treat. 3:467–477. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Wang L, Calcedo R, Nichols TC, et al: Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood. 105:3079–3086. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Flannery JG, Zolotukhin S, Vaquero MI, LaVail MM, Muzyczka N and Hauswirth WW: Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc Natl Acad Sci USA. 94:6916–6921. 1997. View Article : Google Scholar : PubMed/NCBI

35 

Snyder RO and Flotte TR: Production of clinical-grade recombinant adeno-associated virus vectors. Curr Opin Biotechnol. 13:418–423. 2002. View Article : Google Scholar : PubMed/NCBI

36 

Li SF, Wang RZ, Meng QH, et al: Intra-ventricular infusion of rAAV1-EGFP resulted in transduction in multiple regions of adult rat brain: a comparative study with rAAV2 and rAAV5 vectors. Brain Res. 1122:1–9. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Dong JY, Fan PD and Frizzell RA: Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum Gene Ther. 7:2101–2112. 1996. View Article : Google Scholar : PubMed/NCBI

38 

Chiu TL, Lin SZ, Hsieh WH and Peng CW: AAV2-mediated interleukin-12 in the treatment of malignant brain tumors through activation of NK cells. Int J Oncol. 35:1361–1367. 2009.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yiang G, Chou R, Chang W, Wei C and Yu Y: Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death. Mol Clin Oncol 1: 321-325, 2013.
APA
Yiang, G., Chou, R., Chang, W., Wei, C., & Yu, Y. (2013). Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death. Molecular and Clinical Oncology, 1, 321-325. https://doi.org/10.3892/mco.2013.60
MLA
Yiang, G., Chou, R., Chang, W., Wei, C., Yu, Y."Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death". Molecular and Clinical Oncology 1.2 (2013): 321-325.
Chicago
Yiang, G., Chou, R., Chang, W., Wei, C., Yu, Y."Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death". Molecular and Clinical Oncology 1, no. 2 (2013): 321-325. https://doi.org/10.3892/mco.2013.60
Copy and paste a formatted citation
x
Spandidos Publications style
Yiang G, Chou R, Chang W, Wei C and Yu Y: Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death. Mol Clin Oncol 1: 321-325, 2013.
APA
Yiang, G., Chou, R., Chang, W., Wei, C., & Yu, Y. (2013). Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death. Molecular and Clinical Oncology, 1, 321-325. https://doi.org/10.3892/mco.2013.60
MLA
Yiang, G., Chou, R., Chang, W., Wei, C., Yu, Y."Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death". Molecular and Clinical Oncology 1.2 (2013): 321-325.
Chicago
Yiang, G., Chou, R., Chang, W., Wei, C., Yu, Y."Long-term expression of rAAV2-hIL15 enhances immunoglobulin production and lymphokine-activated killer cell-mediated human glioblastoma cell death". Molecular and Clinical Oncology 1, no. 2 (2013): 321-325. https://doi.org/10.3892/mco.2013.60
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