Adenoviral vector–mediated gene transfer of IL-13Rα2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers
Makoto Saito
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorTakashi Murata
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorKen Watanabe
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorKoji Kawakami
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
Search for more papers by this authorMotoyoshi Suzuki
First Department of Internal Medicine, School of Medicine, Yokohama City University, Yokohama, Japan
Search for more papers by this authorTakehiko Koji
Laboratory of Histology and Cell Biology, Department of Developmental and Reconstructive Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorRaj K. Puri
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
Search for more papers by this authorKaio Kitazato
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Nobuyuki Kobayashi
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Fax: +81-95-819-2898.
Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanSearch for more papers by this authorMakoto Saito
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorTakashi Murata
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorKen Watanabe
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorKoji Kawakami
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
Search for more papers by this authorMotoyoshi Suzuki
First Department of Internal Medicine, School of Medicine, Yokohama City University, Yokohama, Japan
Search for more papers by this authorTakehiko Koji
Laboratory of Histology and Cell Biology, Department of Developmental and Reconstructive Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorRaj K. Puri
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
Search for more papers by this authorKaio Kitazato
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Search for more papers by this authorCorresponding Author
Nobuyuki Kobayashi
Laboratory of Molecular Biology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Fax: +81-95-819-2898.
Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanSearch for more papers by this authorAbstract
Previous studies demonstrated that IL-13Rα2 chain–overexpressing cancer cells were highly sensitive to IL-13 cytotoxin (IL13-PE38QQR) and could be targeted by cytotoxin treatment. However, the majority of human tumors do not express high levels of IL-13Rα2 chain. To expand the IL-13 cytotoxin–mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL-13Rα2 chain. We constructed a recombinant adenoviral vector carrying the human IL-13Rα2 gene (Ad-IL-13Rα2), which expresses high levels of IL-13Rα2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL-13Rα2 expression and little sensitivity to IL-13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad-IL-13Rα2 infection. The CC50 of IL-13 cytotoxin for Ad-IL-13Rα2-infected A549 cells was <10 ng/ml, whereas the CC50 for uninfected or control vector-infected cells was >500 ng/ml. We also examined the antitumor activity of IL-13 cytotoxin in an established xenograft model of cytotoxin-resistant human lung tumor. Only a single i.t. injection of Ad-IL-13Rα2 markedly enhanced the sensitivity of established tumors to IL-13 cytotoxin treatment; furthermore, this antitumor effect was significantly sustained for more than 1 month after the last treatment with IL-13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector–mediated IL-13Rα2 gene transfer and IL-13 cytotoxin administration can be an effective targeting approach for several types of IL-13 cytotoxin–resistant cancers which show no or little expression of IL-13Rα2 chain. © 2005 Wiley-Liss, Inc.
References
- 1 Kawakami M, Kawakami K, Kasperbauer JL, Hinkley LL, Tsukuda M, Strome SE, Puri RK. Interleukin-13 receptor α2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Res 2003; 9: 6381–8.
- 2 Debinski W, Gibo DM, Hulet SW, Connor JR, Gillespie GY. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res 1999; 5: 985–90.
- 3 Puri RK, Leland P, Obiri NI, Husain SR, Kreitman RJ, Haas GP, Pastan I, Debinski W. Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR). Blood 1996; 87: 4333–9.
- 4 Murata T, Obiri NI, Debinski W, Puri RK. Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells. Biochem Biophys Res Commun 1997; 238: 90–4.
- 5 Bernard J, Treton D, Vermot-Desroches C, Boden C, Horellou P, Angevin E, Galanaud P, Wijdenes J, Richard Y. Expression of interleukin 13 receptor in glioma and renal cell carcinoma: IL13Rα2 as a decoy receptor for IL13. Lab Invest 2001; 81: 1223–31.
- 6 Debinski W, Obiri NI, Powers SK, Pastan I, Puri RK. Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin. Clin Cancer Res 1995; 1: 1253–8.
- 7 Joshi BH, Plautz GE, Puri RK. Interleukin-13 receptor α chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 2000; 60: 1168–72.
- 8
Husain SR,
Joshi BH,
Puri RK.
Interleukin-13 receptor as a unique target for anti-glioblastoma therapy.
Int J Cancer
2001;
92:
168–75.
10.1002/1097-0215(200102)9999:9999<::AID-IJC1182>3.0.CO;2-N CAS PubMed Web of Science® Google Scholar
- 9 Debinski W, Miner R, Leland P, Obiri NI, Puri RK. Receptor for interleukin (IL) 13 does not interact with IL-4 but receptor for IL-4 interacts with IL-13 on human glioma cells. J Biol Chem 1996; 271: 22428–33.
- 10 Mintz A, Gibo DM, Slagle-Webb B, Christensen ND, Debinski W. IL-13Rα2 is a glioma-restricted receptor for interleukin-13. Neoplasia 2002; 4: 388–99.
- 11 Husain SR, Puri RK. Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft. Blood 2000; 95: 3506–13.
- 12 Husain SR, Obiri NI, Gill P, Zheng T, Pastan I, Debinski W, Puri RK. Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin–based chimeric toxin protein. Clin Cancer Res 1997; 3: 151–6.
- 13 Kawakami K, Kawakami M, Joshi BH, Puri RK. Interleukin-13 receptor–targeted cancer therapy in an immunodeficient animal model of human head and neck cancer. Cancer Res 2001; 61: 6194–200.
- 14 Joshi BH, Kawakami K, Leland P, Puri RK. Heterogeneity in interleukin-13 receptor expression and subunit structure in squamous cell carcinoma of head and neck: differential sensitivity to chimeric fusion proteins comprised of interleukin-13 and a mutated form of Pseudomonas exotoxin. Clin Cancer Res 2002; 8: 1948–56.
- 15
Murata T,
Obiri NI,
Debinski W,
Puri RK.
Human ovarian carcinoma cell lines express IL-4 and IL-13 receptors: comparison between IL-4- and IL-13-induced signal transduction.
Int J Cancer
1997;
70:
230–40.
10.1002/(SICI)1097-0215(19970117)70:2<230::AID-IJC15>3.0.CO;2-M CAS PubMed Web of Science® Google Scholar
- 16 Debinski W, Obiri NI, Pastan I, Puri RK. A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem 1995; 270: 16775–80.
- 17 Maini A, Hillman G, Haas GP, Wang CY, Montecillo E, Hamzavi F, Pontes JE, Leland P, Pastan I, Debinski W, Puri RK. Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin. J Urol 1997; 158: 948–53.
- 18 Husain SR, Puri RK. Interleukin-13 receptor–directed cytotoxin for malignant glioma therapy: from bench to bedside. J Neurooncol 2003; 65: 37–48.
- 19 Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B, Minty C, Casellas P, et al. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 1993; 362: 248–50.
- 20 Wynn TA. IL-13 effector functions. Annu Rev Immunol 2003; 21: 425–56.
- 21 Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science 1998; 282: 2258–61.
- 22 Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, Sheppard D, Mohrs M, Donaldson DD, Locksley RM, Corry DB. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998; 282: 2261–3.
- 23 Kuperman DA, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 2002; 8: 885–9.
- 24 Fallon PG, Richardson EJ, McKenzie GJ, McKenzie AN. Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J Immunol 2000; 164: 2585–91.
- 25 Bancroft AJ, McKenzie AN, Grencis RK. A critical role for IL-13 in resistance to intestinal nematode infection. J Immunol 1998; 160: 3453–61.
- 26 Terabe M, Matsui S, Noben-Trauth N, Chen H, Watson C, Donaldson DD, Carbone DP, Paul WE, Berzofsky JA. NKT cell-mediated repression of tumour immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 2000; 1: 515–20.
- 27 Park JM, Terabe M, van den Broeke LT, Donaldson DD, Berzofsky JA. Unmasking immunosurveillance against a syngeneic colon cancer by elimination of CD4+ NKT regulatory cells and IL-13. Int J Cancer 2005; 114: 80–7.
- 28 Chaouchi N, Wallon C, Goujard C, Tertian G, Rudent A, Caput D, Ferrera P, Minty A, Vazquez A, Delfraissy JF. Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis. Blood 1996; 87: 1022–9.
- 29 Kapp U, Yeh WC, Patterson B, Elia AJ, Kagi D, Ho A, Hessel A, Tipsword M, Williams A, Mirtsos C, Itie A, Moyle M, et al. Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells. J Exp Med 1999; 189: 1939–46.
- 30 Hilton DJ, Zhang JG, Metcalf D, Alexander WS, Nicola NA, Willson TA. Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci USA 1996; 93: 497–501.
- 31 Aman MJ, Tayebi N, Obiri NI, Puri RK, Modi WS, Leonard WJ. cDNA cloning and characterization of the human interleukin 13 receptor α chain. J Biol Chem 1996; 271: 29265–70.
- 32 Miloux B, Laurent P, Bonnin O, Lupker J, Caput D, Vita N, Ferrara P. Cloning of the human IL-13Rα1 chain and reconstitution with the IL-4Rα of a functional IL-4/IL-13 receptor complex. FEBS Lett 1997; 401: 163–6.
- 33 Caput D, Laurent P, Kaghad M, Lelias JM, Lefort S, Vita N, Ferrara P. Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor α chain. J Biol Chem 1996; 271: 16921–6.
- 34 Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O'Hara RMJr, Beier DR, Turner KJ, Wood CR, Collins M. The murine IL-13 receptor α2: molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J Immunol 1998; 161: 2317–24.
- 35 Murata T, Taguchi J, Puri RK. Interleukin-13 receptor α′ but not α chain: a functional component of interleukin-4 receptors. Blood 1998; 91: 3884–91.
- 36 Kawakami K, Taguchi J, Murata T, Puri RK. The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway. Blood 2001; 97: 2673–9.
- 37 Kawakami K, Takeshita F, Puri RK. Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor α2 chain. J Biol Chem 2001; 276: 25114–20.
- 38 Zhang JG, Hilton DJ, Willson TA, McFarlane C, Roberts BA, Moritz RL, Simpson RJ, Alexander WS, Metcalf D, Nicola NA. Identification, purification, and characterization of a soluble interleukin (IL)-13-binding protein. Evidence that it is distinct from the cloned Il-13 receptor and Il-4 receptor α-chains. J Biol Chem 1997; 272: 9474–80.
- 39 Feng N, Lugli SM, Schnyder B, Gauchat JF, Graber P, Schlagenhauf E, Schnarr B, Wiederkehr-Adam M, Duschl A, Heim MH, Lutz RA, Moser R. The interleukin-4/interleukin-13 receptor of human synovial fibroblasts: overexpression of the nonsignaling interleukin-13 receptor α2. Lab Invest 1998; 78: 591–602.
- 40 Wood N, Whitters MJ, Jacobson BA, Witek J, Sypek JP, Kasaian M, Eppihimer MJ, Unger M, Tanaka T, Goldman SJ, Collins M, Donaldson DD, et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor α2. J Exp Med 2003; 197: 703–9.
- 41
Chiaramonte MG,
Mentink-Kane M,
Jacobson BA,
Cheever AW,
Whitters MJ,
Goad ME,
Wong A,
Collins M,
Donaldson DD,
Grusby MJ,
Wynn TA.
Regulation and function of the interleukin 13 receptor α2 during a T helper cell type 2-dominant immune response.
J Exp Med
2003;
197:
687–701.
10.1084/jem.20020903 Google Scholar
- 42 Kawakami K, Kawakami M, Snoy PJ, Husain SR, Puri RK. In vivo overexpression of IL-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Exp Med 2001; 194: 1743–54.
- 43 Trieu Y, Wen XY, Skinnider BF, Bray MR, Li Z, Claudio JO, Masih-Khan E, Zhu YX, Trudel S, McCart JA, Mak TW, Stewart AK. Soluble interleukin-13Rα2 decoy receptor inhibits Hodgkin's lymphoma growth in vitro and in vivo. Cancer Res 2004; 64: 3271–5.
- 44 Kawakami K, Joshi BH, Puri RK. Sensitization of cancer cells to interleukin 13-Pseudomonas exotoxin–induced cell death by gene transfer of interleukin 13 receptor α chain. Hum Gene Ther 2000; 11: 1829–35.
- 45 Kawakami K, Husain SR, Bright RK, Puri RK. Gene transfer of interleukin 13 receptor α2 chain dramatically enhances the antitumor effect of IL-13 receptor–targeted cytotoxin in human prostate cancer xenografts. Cancer Gene Ther 2001; 8: 861–8.
- 46 Kawakami K, Kawakami M, Puri RK. Interleukin-13 receptor-targeted cytotoxin cancer therapy leads to complete eradication of tumors with the aid of phagocytic cells in nude mice model of human cancer. J Immunol 2002; 169: 7119–26.
- 47 Suzuki M, Suzuki S, Yamamoto N, Komatsu S, Inoue S, Hashiba T, Nishikawa M, Ishigatsubo Y. Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice. Hum Gene Ther 2000; 11: 827–38.
- 48 Korst RJ, Bewig B, Crystal RG. In vitro and in vivo transfer and expression of human surfactant SP-A- and SP-B-associated protein cDNAs mediated by replication-deficient, recombinant adenoviral vectors. Hum Gene Ther 1995; 6: 277–87.
- 49 Obiri NI, Leland P, Murata T, Debinski W, Puri RK. The IL-13 receptor structure differs on various cell types and may share more than one component with IL-4 receptor. J Immunol 1997; 158: 756–64.
- 50 Kawakami K, Husain SR, Kawakami M, Puri RK. Improved anti-tumor activity and safety of interleukin-13 receptor targeted cytotoxin by systemic continuous administration in head and neck cancer xenograft model. Mol Med 2002; 8: 487–94.
- 51 Kawakami K, Kawakami M, Puri RK. Specifically targeted killing of interleukin-13 (IL-13) receptor–expressing breast cancer by IL-13 fusion cytotoxin in animal model of human disease. Mol Cancer Ther 2004; 3: 137–47.
- 52 Ye X, Liang M, Meng X, Ren XW, Chen HZ, Li ZY, Ni SH, Lieber A, Hu F. Insulation from viral transcriptional regulatory elements enables improvement to hepatoma-specific gene expression from adenovirus vectors. Biochem Biophys Res Commun 2003; 307: 759–64.
- 53 Zhang M, Li S, Nyati MK, DeRemer S, Parsels J, Rehemtulla A, Ensminger WD, Lawrence TS. Regional delivery and selective expression of a high-activity yeast cytosine deaminase in an intrahepatic colon cancer model. Cancer Res 2003; 63: 658–63.
- 54 Wu L, Matherly J, Smallwood A, Adams JY, Billick E, Belldegrun A, Carey M. Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Gene Ther 2001; 8: 1416–26.
- 55 Takeda T, Inaba H, Yamazaki M, Kyo S, Miyamoto T, Suzuki S, Ehara T, Kakizawa T, Hara M, DeGroot LJ, Hashizume K. Tumor-specific gene therapy for undifferentiated thyroid carcinoma utilizing the telomerase reverse transcriptase promoter. J Clin Endocrinol Metab 2003; 88: 3531–8.
Citing Literature
