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01-09-2010 | Original Article

Enhanced cytotoxicity of IL-24 gene-modified dendritic cells co-cultured with cytokine-induced killer cells to hepatocellular carcinoma cells

Authors: Xin Yu, Wei Xia, Tao Zhang, Hongwei Wang, Yufeng Xie, Jicheng Yang, Jingcheng Miao

Published in: International Journal of Hematology | Issue 2/2010

Abstract

As a novel human cytokine found recently, IL-24 could selectively kill tumor cells by multiple ways. Dendritic cells (DCs) are the major antigen-presenting cells. Recent studies have revealed that IL-24 can promote the antigen-presenting function of DCs. In this study, we evaluated the antitumor effect and mechanism of co-cultured cytokine-induced killer (CIK) cells and autologous DCs modified with IL-24 gene on hepatocellular carcinoma (HCC) cells. DCs and CIK cells were prepared routinely from human peripheral blood mononuclear cells. Recombinant adenovirus AdVGFP/IL-24 (Ad-IL24) was constructed expressing IL-24. IL-24 gene was transduced into DCs via Ad-IL24, the cells obtained were named DC-IL-24. We demonstrated that the expression rates of CD80, CD83, CD1a, HLA-DR, CD40, CXCR4 on DC-IL-24 were significantly increased compared with those of the control group. DC-IL-24 produced markedly higher levels of IL-24, IL-12 and TNF-α as compared with those of DCs. On comparison with non-transfected DCs co-cultured with CIK cells, transfected DCs co-cultured with CIK cells had a significant higher lytic activity against SMMC7721 cells, a HCC cell line.

Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Failure of cancer vaccines: the significant limitations of this approach to immunotherapy. Anticancer Res. 2000;20:2665–76.PubMed

Finkelman FD, Lees A, Birnbaum R, Gause WC, Morris SC. Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J Immunol. 1996;157:1406–14.PubMed

Huang FP, MacPherson GG. Continuing education of the immune system-dendritic cells, immune regulation and tolerance. Curr Mol Med. 2001;1:457–68.CrossRefPubMed

Igney FH, Krammer PH. Tumor counterattack: fact or fiction? Cancer Immunol Immunother. 2005;54:1127–36.CrossRefPubMed

Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 2003;21:807–39.CrossRefPubMed

Whiteside TL. Immune suppression in cancer: effects on immune cells, mechanisms and future therapeutic intervention. Semin Cancer Biol. 2006;16:3–15.CrossRefPubMed

Platsoucas CD, Fincke JE, Pappas J, et al. Immune responses to human tumors: development of tumor vaccines. Anticancer Res. 2003;23:1969–96.PubMed

Rivoltini L, Canese P, Huber V, et al. Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opin Biol Ther. 2005;5:463–76.CrossRefPubMed

Reid DC. Dendritic cells and immunotherapy for malignant disease. Br J Haematol. 2001;112:874–87.CrossRefPubMed

10.

Lebedeva IV, Su ZZ, Chang Y, Kitada S, Reed JC, Fisher PB. The cancer growth suppressing gene mda-7 induces apoptosis selectively in human melanoma cells. Oncogene. 2002;21:708–18.CrossRefPubMed

11.

Saeki T, Mhashilkar A, Chada S, Branch C, Roth JA, Ramesh R. Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro. Gene Ther. 2000;7:2051–7.CrossRefPubMed

12.

Saeki T, Mhashilkar A, Swanson X, et al. Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo. Oncogene. 2002;21:4558–66.CrossRefPubMed

13.

Su Z, Lebedeva IV, Gopalkrishnan RV, et al. A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells. Proc Natl Acad Sci USA. 2001;98:10332–7.CrossRefPubMed

14.

Su ZZ, Lebedeva IV, Sarkar D, et al. Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant gliomas in a p53-independent manner. Oncogene. 2003;22:1164–80.CrossRefPubMed

15.

Caudell EG, Mumm JB, Poindexter N, et al. The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol. 2002;168:6041–6.PubMed

16.

Sarkar D, Su ZZ, Lebedeva IV et al (2002) mda-7 (IL-24): signaling and functional roles. Biotechniques Suppl:30–39

17.

Llovet JM, Beaugrand M. Hepatocellular carcinoma: present status and future prospects. J Hepatol. 2003;38(Suppl 1):S136–49.CrossRefPubMed

18.

Zhu AX. Hepatocellular carcinoma: are we making progress? Cancer Invest. 2003;21:418–28.CrossRefPubMed

19.

Mhashilkar AM, Schrock RD, Hindi M, et al. Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy. Mol Med. 2001;7:271–82.PubMed

20.

Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol. 1994;153:1687–96.PubMed

21.

Jonuleit H, Giesecke-Tuettenberg A, Tuting T, et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer. 2001;93:243–51.CrossRefPubMed

22.

Cranmer LD, Trevor KT, Hersh EM. Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother. 2004;53:275–306.CrossRefPubMed

23.

Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol. 2004;4:941–52.CrossRefPubMed

24.

Pardoll DM. Spinning molecular immunology into successful immunotherapy. Nat Rev Immunol. 2002;2:227–38.CrossRefPubMed

25.

Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol. 2001;2:293–9.CrossRefPubMed

26.

Huang EY, Madireddi MT, Gopalkrishnan RV, et al. Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties. Oncogene. 2001;20:7051–63.CrossRefPubMed

Title: Enhanced cytotoxicity of IL-24 gene-modified dendritic cells co-cultured with cytokine-induced killer cells to hepatocellular carcinoma cells
Authors: Xin Yu
Wei Xia
Tao Zhang
Hongwei Wang
Yufeng Xie
Jicheng Yang
Jingcheng Miao
Publication date: 01-09-2010
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2010
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-010-0654-1

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