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Erschienen in: Cancer Immunology, Immunotherapy 2/2007

01.02.2007 | Original Article

Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin

verfasst von: Hai Lian, Ningyi Jin, Xiao Li, Zhiqiang Mi, Jingmin Zhang, Lili Sun, Xuemei Li, Hongling Zheng, Ping Li

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2007

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Abstract

Immunization strategies using plasmid DNA can potentially improve humoral and cellular immune responses that protect against cancer and infectious diseases. The chicken anemia virus-derived Apoptin protein exhibits remarkable specificity in its ability to induce apoptosis in tumor cells, but not in normal diploid cells. Interleukin-18 (IL-18) is a Th1-type cytokine that has demonstrated potential as a biological adjuvant in murine tumor models. In this study, we analyzed the anti-tumor potential and mechanism of action of simultaneous Apoptin and IL-18 gene transfer in C57BL/6 mice bearing Lewis lung carcinoma (LLC). Here we report that the growth of established tumors in mice immunized with pAPOPTIN in conjunction with pIL-18 was significantly inhibited compared with the growth of tumors in mice immunized with the empty vector (EV) or pAPOPTIN alone. Furthermore, the immunization of mice with pAPOPTIN in conjunction with pIL-18 elicited strong natural killer activity and LLC tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro. In addition, T cells from lymph nodes of mice vaccinated with pIL-18 or pAPOPTIN + pIL-18 secreted high levels of the Th1 cytokine IL-2 and IFN-γ, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with Apoptin together with IL-18 may be a novel and powerful strategy for cancer immunotherapy.
Literatur
1.
Zurück zum Zitat (2002) Chemotherapy and non-small-cell lung cancer. Drug Ther Bull 40:9–11 (2002) Chemotherapy and non-small-cell lung cancer. Drug Ther Bull 40:9–11
2.
Zurück zum Zitat Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D (2000) Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 18:623–631PubMed Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D (2000) Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 18:623–631PubMed
3.
Zurück zum Zitat Rana SN, Li X, Chaudry IH, Bland KI, Choudhry MA (2005) Inhibition of IL-18 reduces myeloperoxidase activity and prevents edema in intestine following alcohol and burn injury. J Leukoc Biol 77:719–728PubMedCrossRef Rana SN, Li X, Chaudry IH, Bland KI, Choudhry MA (2005) Inhibition of IL-18 reduces myeloperoxidase activity and prevents edema in intestine following alcohol and burn injury. J Leukoc Biol 77:719–728PubMedCrossRef
4.
Zurück zum Zitat Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH (2000) Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18:122–130PubMed Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH (2000) Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18:122–130PubMed
5.
Zurück zum Zitat ten Bokkel Huinink WW, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen PL, Liippo K, Mattson K, von Pawel J, Ricci S, Sederholm C, Stahel RA, Wagenius G, Walree NV, Manegold C (1999) Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer 26:85–94PubMedCrossRef ten Bokkel Huinink WW, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen PL, Liippo K, Mattson K, von Pawel J, Ricci S, Sederholm C, Stahel RA, Wagenius G, Walree NV, Manegold C (1999) Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer 26:85–94PubMedCrossRef
6.
Zurück zum Zitat Hu W, Kavanagh JJ (2003) Anticancer therapy targeting the apoptotic pathway. Lancet Oncol 4:721–729PubMedCrossRef Hu W, Kavanagh JJ (2003) Anticancer therapy targeting the apoptotic pathway. Lancet Oncol 4:721–729PubMedCrossRef
7.
Zurück zum Zitat Danen-Van Oorschot AA, Zhang YH, Leliveld SR, Rohn JL, Seelen MC, Bolk MW, Van Zon A, Erkeland SJ, Abrahams JP, Mumberg D, Noteborn MH (2003) Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. J Biol Chem 278:27729–27736PubMedCrossRef Danen-Van Oorschot AA, Zhang YH, Leliveld SR, Rohn JL, Seelen MC, Bolk MW, Van Zon A, Erkeland SJ, Abrahams JP, Mumberg D, Noteborn MH (2003) Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. J Biol Chem 278:27729–27736PubMedCrossRef
8.
Zurück zum Zitat Oro C, Jans DA (2004) The tumour specific pro-apoptotic factor apoptin (Vp3) from chicken anaemia virus. Curr Drug Targets 5:179–190PubMedCrossRef Oro C, Jans DA (2004) The tumour specific pro-apoptotic factor apoptin (Vp3) from chicken anaemia virus. Curr Drug Targets 5:179–190PubMedCrossRef
9.
Zurück zum Zitat Poon IK, Oro C, Dias MM, Zhang J, Jans DA (2005) Apoptin nuclear accumulation is modulated by a CRM1-recognized nuclear export signal that is active in normal but not in tumor cells. Cancer Res 65:7059–7064PubMedCrossRef Poon IK, Oro C, Dias MM, Zhang J, Jans DA (2005) Apoptin nuclear accumulation is modulated by a CRM1-recognized nuclear export signal that is active in normal but not in tumor cells. Cancer Res 65:7059–7064PubMedCrossRef
10.
Zurück zum Zitat Maddika S, Booy EP, Johar D, Gibson SB, Ghavami S, Los M (2005) Cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway. J Cell Sci 118:4485–4493PubMedCrossRef Maddika S, Booy EP, Johar D, Gibson SB, Ghavami S, Los M (2005) Cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway. J Cell Sci 118:4485–4493PubMedCrossRef
11.
Zurück zum Zitat Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4:11–22PubMedCrossRef Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4:11–22PubMedCrossRef
12.
Zurück zum Zitat Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378:88–91PubMedCrossRef Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378:88–91PubMedCrossRef
13.
Zurück zum Zitat Micallef MJ, Yoshida K, Kawai S, Hanaya T, Kohno K, Arai S, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Kurimoto M (1997) In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites. Cancer Immunol Immunother 43:361–367PubMedCrossRef Micallef MJ, Yoshida K, Kawai S, Hanaya T, Kohno K, Arai S, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Kurimoto M (1997) In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites. Cancer Immunol Immunother 43:361–367PubMedCrossRef
14.
Zurück zum Zitat Osaki T, Peron JM, Cai Q, Okamura H, Robbins PD, Kurimoto M, Lotze MT, Tahara H (1998) IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects. J Immunol 160:1742–1749PubMed Osaki T, Peron JM, Cai Q, Okamura H, Robbins PD, Kurimoto M, Lotze MT, Tahara H (1998) IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects. J Immunol 160:1742–1749PubMed
15.
Zurück zum Zitat Marshall DJ, Rudnick KA, McCarthy SG, Mateo LR, Harris MC, McCauley C, Snyder LA (2006) Interleukin-18 enhances Th1 immunity and tumor protection of a DNA vaccine. Vaccine 24:244–253PubMedCrossRef Marshall DJ, Rudnick KA, McCarthy SG, Mateo LR, Harris MC, McCauley C, Snyder LA (2006) Interleukin-18 enhances Th1 immunity and tumor protection of a DNA vaccine. Vaccine 24:244–253PubMedCrossRef
16.
Zurück zum Zitat Nakamura S, Otani T, Ijiri Y, Motoda R, Kurimoto M, Orita K (2000) IFN-gamma-dependent and -independent mechanisms in adverse effects caused by concomitant administration of IL-18 and IL-12. J Immunol 164:3330–3336PubMed Nakamura S, Otani T, Ijiri Y, Motoda R, Kurimoto M, Orita K (2000) IFN-gamma-dependent and -independent mechanisms in adverse effects caused by concomitant administration of IL-18 and IL-12. J Immunol 164:3330–3336PubMed
17.
Zurück zum Zitat Tan F, Zhang Y, Xu Y, Liu W, Zhang Y, Ouyang H (1998) Amplification and cloning of genomic DNA of apoptin. Chin J Vet Sci 18:421–423 Tan F, Zhang Y, Xu Y, Liu W, Zhang Y, Ouyang H (1998) Amplification and cloning of genomic DNA of apoptin. Chin J Vet Sci 18:421–423
18.
Zurück zum Zitat Mi Z, Jin N, Gong W, Xue L, Lian H, Xie L, Li P (2003) Construction and expression of the nucleic acid vaccine pVVP3 and pVHN and its effect on tumor cell. Chin J Biochem Mol Biol 19:704–708 Mi Z, Jin N, Gong W, Xue L, Lian H, Xie L, Li P (2003) Construction and expression of the nucleic acid vaccine pVVP3 and pVHN and its effect on tumor cell. Chin J Biochem Mol Biol 19:704–708
19.
Zurück zum Zitat Wu J, Wu Y, Yang BB (2002) Anticancer activity of Hemsleya amabilis extract. Life Sci 71:2161–2170PubMedCrossRef Wu J, Wu Y, Yang BB (2002) Anticancer activity of Hemsleya amabilis extract. Life Sci 71:2161–2170PubMedCrossRef
20.
Zurück zum Zitat Kiechle FL, Malinski T (1993) Nitric oxide: biochemistry, pathophysiology, and detection. Am J Clin Pathol 100:567–575PubMed Kiechle FL, Malinski T (1993) Nitric oxide: biochemistry, pathophysiology, and detection. Am J Clin Pathol 100:567–575PubMed
21.
Zurück zum Zitat Dasgupta S, Tripathi PK, Bhattacharya-Chatterjee M, O’Malley BW Jr, Chatterjee SK (2003) Recombinant vaccinia virus expressing IL-2 generates effective anti-tumor responses in an orthotopic murine model of head and neck carcinoma. Mol Ther 8:238–248PubMedCrossRef Dasgupta S, Tripathi PK, Bhattacharya-Chatterjee M, O’Malley BW Jr, Chatterjee SK (2003) Recombinant vaccinia virus expressing IL-2 generates effective anti-tumor responses in an orthotopic murine model of head and neck carcinoma. Mol Ther 8:238–248PubMedCrossRef
22.
Zurück zum Zitat Fischer U, Schulze-Osthoff K (2005) New approaches and therapeutics targeting apoptosis in disease. Pharmacol Rev 57:187–215PubMedCrossRef Fischer U, Schulze-Osthoff K (2005) New approaches and therapeutics targeting apoptosis in disease. Pharmacol Rev 57:187–215PubMedCrossRef
23.
Zurück zum Zitat van der Eb MM, Pietersen AM, Speetjens FM, Kuppen PJ, van de Velde CJ, Noteborn MH, Hoeben RC (2002) Gene therapy with apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther 9:53–61PubMedCrossRef van der Eb MM, Pietersen AM, Speetjens FM, Kuppen PJ, van de Velde CJ, Noteborn MH, Hoeben RC (2002) Gene therapy with apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther 9:53–61PubMedCrossRef
24.
Zurück zum Zitat Guelen L, Paterson H, Gaken J, Meyers M, Farzaneh F, Tavassoli M (2004) TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. Oncogene 23:1153–1165PubMedCrossRef Guelen L, Paterson H, Gaken J, Meyers M, Farzaneh F, Tavassoli M (2004) TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. Oncogene 23:1153–1165PubMedCrossRef
25.
Zurück zum Zitat Pietersen AM, van der Eb MM, Rademaker HJ, van den Wollenberg DJ, Rabelink MJ, Kuppen PJ, van Dierendonck JH, van Ormondt H, Masman D, van de Velde CJ, van der Eb AJ, Hoeben RC, Noteborn MH (1999) Specific tumor-cell killing with adenovirus vectors containing the apoptin gene. Gene Ther 6:882–892PubMedCrossRef Pietersen AM, van der Eb MM, Rademaker HJ, van den Wollenberg DJ, Rabelink MJ, Kuppen PJ, van Dierendonck JH, van Ormondt H, Masman D, van de Velde CJ, van der Eb AJ, Hoeben RC, Noteborn MH (1999) Specific tumor-cell killing with adenovirus vectors containing the apoptin gene. Gene Ther 6:882–892PubMedCrossRef
26.
Zurück zum Zitat Wallace-Brodeur RR, Lowe SW (1999) Clinical implications of p53 mutations. Cell Mol Life Sci 55:64–75PubMedCrossRef Wallace-Brodeur RR, Lowe SW (1999) Clinical implications of p53 mutations. Cell Mol Life Sci 55:64–75PubMedCrossRef
27.
Zurück zum Zitat Reed JC (1995) Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am 9:451–473PubMed Reed JC (1995) Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am 9:451–473PubMed
28.
Zurück zum Zitat Hickman JA, Potten CS, Merritt AJ, Fisher TC (1994) Apoptosis and cancer chemotherapy. Philos Trans R Soc Lond B Biol Sci 345:319–325PubMed Hickman JA, Potten CS, Merritt AJ, Fisher TC (1994) Apoptosis and cancer chemotherapy. Philos Trans R Soc Lond B Biol Sci 345:319–325PubMed
29.
Zurück zum Zitat Nakamura K, Okamura H, Wada M, Nagata K, Tamura T (1989) Endotoxin-induced serum factor that stimulates gamma interferon production. Infect Immun 57:590–595PubMed Nakamura K, Okamura H, Wada M, Nagata K, Tamura T (1989) Endotoxin-induced serum factor that stimulates gamma interferon production. Infect Immun 57:590–595PubMed
30.
Zurück zum Zitat Fukumoto H, Nishio M, Nishio K, Heike Y, Arioka H, Kurokawa H, Ishida T, Fukuoka K, Nomoto T, Ohe Y, Saijo N (1997) Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo. Jpn J Cancer Res 88:501–505PubMed Fukumoto H, Nishio M, Nishio K, Heike Y, Arioka H, Kurokawa H, Ishida T, Fukuoka K, Nomoto T, Ohe Y, Saijo N (1997) Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo. Jpn J Cancer Res 88:501–505PubMed
31.
Zurück zum Zitat Hashimoto W, Osaki T, Okamura H, Robbins PD, Kurimoto M, Nagata S, Lotze MT, Tahara H (1999) Differential antitumor effects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas–Fas ligand- and perforin-induced tumor apoptosis, respectively. J Immunol 163:583–589PubMed Hashimoto W, Osaki T, Okamura H, Robbins PD, Kurimoto M, Nagata S, Lotze MT, Tahara H (1999) Differential antitumor effects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas–Fas ligand- and perforin-induced tumor apoptosis, respectively. J Immunol 163:583–589PubMed
32.
Zurück zum Zitat Colombo MP, Trinchieri G (2002) Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 13:155–168PubMedCrossRef Colombo MP, Trinchieri G (2002) Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 13:155–168PubMedCrossRef
33.
Zurück zum Zitat Smyth MJ, Taniguchi M, Street SE (2000) The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol 165:2665–2670PubMed Smyth MJ, Taniguchi M, Street SE (2000) The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol 165:2665–2670PubMed
34.
Zurück zum Zitat Dasgupta S, Bhattacharya-Chatterjee M, O’Malley BW Jr, Chatterjee SK (2006) Recombinant vaccinia virus expressing interleukin-2 invokes anti-tumor cellular immunity in an orthotopic murine model of head and neck squamous cell carcinoma. Mol Ther 13:183–193PubMedCrossRef Dasgupta S, Bhattacharya-Chatterjee M, O’Malley BW Jr, Chatterjee SK (2006) Recombinant vaccinia virus expressing interleukin-2 invokes anti-tumor cellular immunity in an orthotopic murine model of head and neck squamous cell carcinoma. Mol Ther 13:183–193PubMedCrossRef
35.
Zurück zum Zitat Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, Bordignon C, Traversari C (2000) Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response. Proc Natl Acad Sci USA 97:2185–2190PubMedCrossRef Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, Bordignon C, Traversari C (2000) Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response. Proc Natl Acad Sci USA 97:2185–2190PubMedCrossRef
36.
Zurück zum Zitat Sin JI, Kim JJ, Boyer JD, Ciccarelli RB, Higgins TJ, Weiner DB (1999) In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model. J Virol 73:501–509PubMed Sin JI, Kim JJ, Boyer JD, Ciccarelli RB, Higgins TJ, Weiner DB (1999) In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model. J Virol 73:501–509PubMed
37.
Zurück zum Zitat Woldbaek PR, Tonnessen T, Henriksen UL, Florholmen G, Lunde PK, Lyberg T, Christensen G (2003) Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse: a potential role in cardiac dysfunction. Cardiovasc Res 59:122–131PubMedCrossRef Woldbaek PR, Tonnessen T, Henriksen UL, Florholmen G, Lunde PK, Lyberg T, Christensen G (2003) Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse: a potential role in cardiac dysfunction. Cardiovasc Res 59:122–131PubMedCrossRef
38.
Zurück zum Zitat Triccas JA, Sun L, Palendira U, Britton WJ (2002) Comparative effects of plasmid-encoded interleukin 12 and interleukin 18 on the protective efficacy of DNA vaccination against Mycobacterium tuberculosis. Immunol Cell Biol 80:346–350PubMedCrossRef Triccas JA, Sun L, Palendira U, Britton WJ (2002) Comparative effects of plasmid-encoded interleukin 12 and interleukin 18 on the protective efficacy of DNA vaccination against Mycobacterium tuberculosis. Immunol Cell Biol 80:346–350PubMedCrossRef
Metadaten
Titel
Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin
verfasst von
Hai Lian
Ningyi Jin
Xiao Li
Zhiqiang Mi
Jingmin Zhang
Lili Sun
Xuemei Li
Hongling Zheng
Ping Li
Publikationsdatum
01.02.2007
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 2/2007
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0178-y

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