Dokument: Triple Level Targeting zur zielgerichteten Virotherapie beim Mammakarzinom
| Titel: | Triple Level Targeting zur zielgerichteten Virotherapie beim Mammakarzinom | |||||||
| Weiterer Titel: | Triple Level Targeting for Virotherapy of Breast Cancer | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=34264 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20150601-102946-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Creutz, Heike [Autor] | |||||||
| Dateien: |
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| Beitragende: | PD Dr. Dr. Bauerschmitz, Gerd [Gutachter] Prof. Dr. Höhn [Gutachter] | |||||||
| Stichwörter: | Virotherapie, Mammakarzinom, Triple Level Targeting | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Das Mamma-Karzinom ist mit 27,8% der häufigste maligne Tumor der Frau in den westlichen Industrienationen, jede 8. bis 10. Frau ist betroffen (1). Innerhalb des breit gefächerten Spektrums von Erkrankungsrisiken wie frühe Menarche und späte Menopause, positive Familienanamnese (Nachweis von BRCA1 und BRCA2), späte erste Schwangerschaft oder Kinderlosigkeit, westliche Lebensweise, Hormontherapie mit Östrogenen, Übergewicht, atypisch proliferierende Mastopathie, Alkohol- und Nikotinabusus ist derzeit das fortgeschrittene Lebensalter als wesentlichster Faktor einzustufen. In Hinblick auf die ansteigende Lebenserwartung in den Industrieländern gewinnt dieses Risiko kontinuierlich an Bedeutung.
Aufgrund ausgedehnter Vorsorgeuntersuchungen und modifizierter Früherkennungs-angeboten, insbesondere der Mammographie, hat sich die Mortalitätsrate im Jahr 2003 in Europa mit 26,5%/100.000 Fälle gegenüber 1997 mit 30,3%/100.000 Fälle leicht gesenkt (1). Männer erkranken im Durchschnitt 10 Jahre später als Frauen an einem Mamma-Karzinom, die Inzidenz liegt bei ca. 400 Fällen pro Jahr. Weltweit waren im Jahr 2004 insgesamt 275.000 Frauen betroffen (4) (IARC, International Agency for Research of Cancer). Wenn auch die bekannten konventionellen Therapiemethoden wie Hormon-, Chemo- und Strahlentherapie signifikante Erfolge in der Behandlung des Mammakarzinoms erzielt haben, liegt die 5-Jahres-Überlebensrate zur Zeit stagnierend bei 81% (2008) und hat sich damit gegenüber dem Jahr 2002 nur minimal, d. h. um 3%, erhöht (3, 5) (Tab. 1). Während die Zahl an Neuerkrankungen bei Brustkrebs weiter ansteigt, nimmt die Mortalität seit Mitte der 90er Jahre leicht ab. So erreichte man mit etablierten Therapieverfahren bereits eine deutliche Verbesserung der Überlebensraten. Molekulargenetische Verfahren könnten zukünftig im Sinne einer selektiven viralen Onkolyse an diesem Punkt viel versprechende Ansätze für neue Therapieformen bieten. In dieser Doktorarbeit zeigen Funktionsanalysen von zwei modifizierten Adenovirus-Vektoren die potentielle Wirksamkeit der Adenovirotherapie als neue, ergänzende Therapieform beim Mamma-Karzinom. Möglicherweise werden im Zuge der Virotherapie als neuartiges Therapieverfahren weitere Erfolge verzeichnet und die Überlebenschancen weiterhin verbessert werden können.Using conditionally replicative adenoviruses (CRAds) represent a therapeutic method to achieve efficient tumor cell oncolysis and mitigate the limitations of tumor infection. Ideally, cancer specific replication of CRAds results in viral mediated oncolysis of infected tumor tissues and release of the virus progeny, capable of further propagating in surrounding tumor cells but not in those of normal tissues. A number of characteristics of the Adenovirus type 5 (Ad5) make it an optimal gene therapy/virotherapy vector suitable for a wide array of cancer therapeutic approaches. Despite these advantages, overall efficiancy of Ad5-based cancer gene therapy/virotherapy approaches remains limited by sub-optimal vector delivery efficiency in cancer tissues and non-specific delivery to normal tissues. The ability of CRAds and other replicative agents to eradicate tumors critically depends on two key functions, efficient replication and spread within the tumor. A monitoring system that can capture quantitatively and dynamically the replication and spread of these oncolytic viruses would be a useful assessment tool for developing these agents as well as for their application in patients. The labeling system should also reflect the replication, lysis and dispersion efficiency of the virus. Recent work by several groups has defined the C-terminus of the minor capsid protein pIX as a locus capable of presenting incorporated ligands on the virus surface. In this study, two CRAd vectors labeled with the fluorescent capsid fusion protein IX-red fluorescent protein (pIX-EGFP) were developed. Expression of the fluorescent fusion-protein label in infected cells could be detected. The labeled virions could be visualized by fluorescence microscopy and quantified by flow cytometry. These results were applicable to the tracking of CRAd infection, as well as localizing the distribution of the vector in tissues. Expression of pIX-RFP could be exploited to detect the replication and spread of CRAds. These results indicate that pIX can serve a platform for incorporation of heterologues proteins in the context of a replicating adenovirus. It is believed that capsid-labeled CRAds have utility for vector-development studies and for monitoring CRAd-based oncolytic adenovirus replication. Introduction Breast-cancer is the most frequent cancer of women worldwide. While conventional adjuvant and neoadjuvant therapys are limited to increase survival rates, gene therapy/adenotherapy using Ad5/3 offers new approaches for therapeutical treatments. One approach, also useful in regard of any other cancer therapys, is the development of CRAds, conditionally replicative virus. A CRAd itself is the anticancer agent. (1,8) Virotherapy exploits the ability of the virus to kill tumor cells by oncolysis. Moreover CRAds should be able to disguise cancer cells from normal tissues to spread in cancer cells but to avoid infectivity in normal epithelian cells to minimize side effects because of backround activity like liver toxicity. Transductional , transcriptional and translational targeting deliver a new and promising approach to use selective adenoviral replication in breast cancer cells, but to spare surrounding tissues.(1,8) But the application of adenoviruses is limited by a missing proof of their trail of infectivity. The development of CRAd-vectors, labelling structure protein pIX on the surface of the adenovirus with RFP shows us quantitatively and dynamically their effect on cancer cells. That means, through direct labelling the vectors with detectable RFP allows to localize them in cells.(1) In the past it was shown that the DNA-replication and other cytopathological effects were not affected while DNA-packaging and thermostability were marginally influenced.(3) In this study we could show the intact infectivity of these genetically engineered viruses by visualizing and quantifying MB-435s cells by microscopy and flow-cytometrie. | |||||||
| Quelle: | Quellenverzeichnis
1. Husmann G, Kaatsch P, Katalinic A, Bertz J, Haberland J, Kraywinkel K, Wolf U, „Krebs in Deutschland Häufigkeiten und Trends, Robert-Koch-Institut und Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V.“, Beiträge zur Gesundheitsberichtserstattung des Bundes, 7.Auflage, 56-59, 2005/2006 2. Kraywinkel K, Batzler WU, Bertram H, Hense HW, „Epidemiologisches Krebsregister“ Schwerpunktbericht Brustkrebs“, 13-20, 1992-2004 3. Malek D, Rabe P, „Ergebnisse des Mammographie-Screening-Programms in Deutschland, Evaluationsbericht“, BMG, BMU, Kooperationsgemeinschaft Mammographie, 24-26 und 35-50, 2008-2009 4. Boyle P, Ferlay J, “Cancer incidence and mortality in Europe 2004”, IARC, International Agency for Research of Cancer, Lyon, France, Annals of Oncology, 481-488, 16/2005 5. Becker N, Wahrendorf J, „DKFZ, Deutsches Krebsforschungszentrum“, Krebsdatlas der Bundesrepublik Deutschland“, Springer Berlin Heidelberg New York, 1998 6. Bauerschmitz GJ, Lam JT, Kanerva A et al., „Treatment of ovarian cancer with a tropism modified oncolytic adenovirus“, Cancer Res., 1266-70, 62/2002b 7. Douglas JT, Curie Dl, “Adenoviral vectors for gene therapy”, Mol Biotechnol 36(1), 71-80, 2007 8. Zhu ZB, Makhija SK, Lu B, Wang M, Kaliberova L, Liu B, Rivera AA, Nettelbeck DM, Mahasreshti PJ, Leath CA, Yamaoto M, Alvarez AD, Curiel D, “Transcriptionel targeting of adenoviral vector through the CXCR4 tumor-specific promoter”, Gene Therapy, 645-648, 11/2004 9. Stoff-Khalili MA, Rivera A, Nedeljkovic-Kurepa A, DeBenedetti A, Li XL, Odaka Y, Podduturi J, Sibley DA, Siegal GP, Stoff A, Young S, Zhu ZB, Curiel DT, Mathis JM, "Cancer-specific targeting of a conditionally replicative adenovirus using mRNA translational control", Breast Cancer Res Treat 108(1), 43-55, 2008 Mar. 10. Vellinga J, Rabelink Matijn JW, Cramer SJ, van den Wollenberg Diana JM, Van der Meulen H, Leppard KN, Fallaux FJ, Hoeben RC, “Spacers increase the Accessability Peptide Ligands linked to the Carboxyl Terminus of Adenovirus Minor Capsid Protein IX”, J Virol, 78(7), 3470-3479, 04/2004 11. Yu W, Fang H, “Clinical trials with oncolytic adenovirus in China”, Curr Cancer Drug Targets, 141-148, 7/2007 12. Stoff-Khalili MA, Rivera AA, Nedeljkovic-Kurepa A, DeBenedetti A, Li XL, Odaka Y, Podduturi J, Sibley DA, Siegal GP, Stoff A, Young S, Zhu ZB, Curiel DT, Mathis JM; “Cancer-specific targeting of a conditionally replicative adenovirus using mRNA translational control”, Breast Cancer Res Treat., 108/1, 43-55, 03/2008 13. Mishra R, Miyamoto M, Yoshioka T, Ishikawa K, Matsumura Y, Shoji Y, Ichinokawa K, Itoh T, Shichinohe T, Hirano S, Kondo S, “Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo”, Int J Oncol., 34(5), 1231-40, 05/2009 14. Kruyt FA, Curiel DT, “Toward a new generation of conditionally replicating adenoviruses: pairing tumor selectivity with maximal oncolysis (review)”, Hum Gene Ther., 1;13(4), 485-95, 03/2002 15. Coughlan L, Alba R, Parker AL, Bradshaw AC, McNeish IA, Nicklin SA, Baker AH, “Tropism-modification strategies for targeted gene delivery using adenoviral vectors”, Viruses, 2(10), 290-355, 2010 Oct. 16. Bauerschmitz GJ, Barker SD, Hemminki A., “Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents (review)”, Int J Oncol. 21(6), 1161-74, 12/2002 17. Nieto Y, Cagnoni PJ, Nawaz S, Shpall EJ, Yerushalmi R, Cook B, Russell P, Mc Dermit J, Murphy J, Bearman SI, Jones RB, “Evaluation of the predictive value of Her-2/neu overexpression and p53 mutations in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplantation”, J Clin Oncol, 2070-2080, 18/2000 18. Casado E, Nettelbeck DM, Gomez-Navarro J, Hemminki A, Gonzalez Baron M., Siegal GP, Barnes MN, Alvarez RD, Curiel DT, “Transcriptional targeting for ovarian cancer gene therapy”, Gynecol Oncol, 229-237, 82/2001 19. Elshami AA, Saavedra A, Zhang H, Kucharczuk JC, Spray DC, Fishman GI, Amin KM, Kaiser LR, Albelda SM, “Gap junctions play a role in the 'bystander effect' of the herpes simplex virus thymidine kinase/ganciclovir system in vitro”, Gene Ther 3:85-92, 1996 20. Nishida Y, Maeda Y, Hara A, Arima T, Kimura E, Yamashita S, Uyama E, Mita S, Uchino M, “Adenovirus-mediated murine interferon-gamma 82 receptor transfer enhances the efficacy of IFN-gamma in vivo”, Biochem Biophys Res Commun, 290:1042-1047, 2002 21. Jocham D, Richter A, Hoffmann L, Iwig K, Fahlenkamp D, Zakrzewski G, Schmitt E, Dannenberg T, Lehmacher W, von Wietersheim J, Doehn C, “Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial”, Lancet, 363:594-599, 2004 22. Duverger V, Sartorius U, Klein-Bauernschmitt P, Krammer PH, Schlehofer JR, “Enhancement of cisplatin-induced apoptosis by infection with adeno-associated virus type 2”, Int J Cancer, 97: 706-712, 2002 23. Schiedlmeier B, Schilz AJ, Kuhlcke K, Laufs S, Baum C, Zeller WJ, Eckert HG, Fruehauf S, “Multidrug resistance 1 gene transfer can confer chemoprotection to human peripheral blood progenitor cells engrafted in immunodeficient mice”, Hum Gene Ther, 13:233-242, 2002 24. Ponnazhagan S, Curiel DT, Shaw DR, Alvarez RD, Siegal GP, “Adeno-associated virus for cancer gene therapy”, Cancer Res, 61:6313-6321, 2001 25. Vermeij J, Zeinoun Z, Neyns B, Teugels E, Bourgain C, De Greve J, “Transduction of ovarian cancer cells: a recombinant adeno-associated viral vector compared to an adenoviral vector”, Br J Cancer, 85:1592-1599, 2001 26. Miller DG, Rutledge EA, Russell DW, “Chromosomal effects of adeno-associated virus vector integration”, Nat Genet, 30:147-148, 2002 27. Rochlitz CF, “Gene therapy of cancer”, Swiss Med Wkly, 131: 4-9,83, 2001 28. Lee SG, Yoon SJ, Kim CD, Kim K, Lim DS, Yeom YI, Sung MW, Heo DS, Kim NK, “Enhancement of adenoviral transduction with polycationic liposomes in vivo”, Cancer Gene Ther, 7:1329-1335, 2000 29. Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E, Reynolds TC, Murray JL, “Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer”, Clin Cancer Res, 7:1237-1245, 2001 30. Wang SC, Zhang L, Hortobagyi GN, Hung MC, “Targeting HER2: recent developments and future directions for breast cancer patients”, Semin Oncol, 28:21-29, 2001 31. Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL, Valero V, Gershenson DM, Bevers MW., Huang L, Lopez-Berestein G, Hung MC, “Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial”, J Clin Oncol, 19:3422-3433, 2001 32. Chon HS, Hu W, Kavanagh JJ, “Targeted therapies in gynaecologic cancers”, Curr Cancer Drug Targets, 6:333-363, 2006 33. Cross D, Burmester JK, “Gene therapy for cancer treatment: past, present and future”, Clin Med Res, 4:218-227, 2006 34. Nakayama M, Both GW, Banizs B, Tsuruta Y, Yamamoto S, Kawakami Y, Douglas JT, Tani K, Curiel DT, Glasgow JN, “An adenovirus serotype 5 vector with fibers derived from ovine atadenovirus demonstrates CAR-independent tropism and unique biodistribution in mice”, Virology, 350(1):103-15, 2006 Jun 20 35. Bauerschmitz GJ, Guse K, Kanerva A, Menzel A, Herrmann I, Desmond RA, Yamamoto M, Nettelbeck DM, Hakkarainen T, Dall P, Curiel DT, Hemminki A, “Triple-targeted oncolytic adenoviruses featuring the cox2 promoter, E1A transcomplementation, and serotype chimerism for enhanced selectivity for ovarian cancer cells”, Mol Ther, 14:164- 174, 2006 36. Stoff-Khalili MA, Rivera AA, Stoff A, Michael Mathis J, Rocconi RP, Matthews QL, Numnum MT, Herrmann I, Dall P, Eckhoff DE, Douglas JT, Siegal GP, Zhu ZB, Curiel DT, “Combining high selectivity of replication via CXCR4 promoter with fiber chimerism for effective adenoviral oncolysis in breast cancer”, Int J Cancer,120(4):935-41, 2007 Feb 15 37. Stoff-Khalili MA, Rivera AA, Nedeljkovic-Kurepa A, DeBenedetti A, Li XL, Odaka Y, Podduturi J, Sibley DA, Siegal GP, Stoff A, Young S, Zhu ZB, Curiel DT, Mathis JM, “Cancer-specific targeting of a conditionally replicative adenovirus using mRNA translational control”, Breast Cancer Res Treat. 108(1):43-55, 2008 Mar 38. Database, C. T. http://www.clinicaltrials.gov/ct/action/GetStudy. 2006 39. Dmitriev I, Kashentseva E, Rogers BE, Krasnykh V, Curiel DT, “Ectodomain of coxsackievirus and adenovirus receptor genetically fused to epidermal growth factor mediates adenovirus targeting to epidermal growth factor receptor-positive cells”, J Virol, 74:6875-6884, 2000 40. Kanerva A, Wang M, Bauerschmitz GJ, Lam JT, Desmond RA, Bhoola SM, Barnes MN, Alvarez RD, Siegal GP, Curiel DT, Hemminki A, “Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses”, Mol Ther, 5:695-704, 2000 41. Kanerva A, Mikheeva GV, Krasnykh V, Coolidge CJ, Lam JT, Mahasreshti PJ, Barker SD, Straughn M, Barnes MN, Alvarez RD, Hemminki A, Curiel DT, “Targeting adenovirus to the serotype 3 receptor increases gene transfer efficiency to ovarian cancer cells”, Clin Cancer Res, 8:275-280, 2002 42. Tanaka T, Kanai F, Lan KH, Ohashi M, Shiratori Y, Yoshida Y, Hamada H, Omata M, “Adenovirus-mediated gene therapy of gastric carcinoma using cancer-specific gene expression in vivo”, Biochemical & Biophysical Research Communications, 231:775-779, 1997 43. Yamamoto M, Alemany R, Adachi Y, Grizzle WE, Curiel DT, “Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers”, Mol Ther, 3:385-394, 2001 44. Lehnert M, “Clinical multidrug resistance in cancer: a multifactorial problem”, Eur J Cancer, 32A:912-920, 1996 45. Holzmayer TA, Hilsenbeck S, von Hoff DD, Robinson I, “Clinical Correlates of MDR1 (P-Glycoprotein) Gene Expression in Ovarian and Small-cell Lung Carcinomas”, J Natl Cancer Inst, 84(19):1486-1491, 1992 46. Baekelandt MM, Holm R, Nesland JM, Tropé CG, Kristensen GB, “P-Glycoprotein Expression is a Marker for Chemotherapy Resistance and Prognosis in Advanced Ovarian Cancer”, Anticancer Res, 20:1061-1067, 2000 47. Walther W, Wendt J, Stein U, “Employment of the mdr1 promoter for the chemotherapy-inducible expression of therapeutic genes in cancer gene therapy”, Gene Therapy, 4:544-552, 1997 48. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F, “An adenovirus mutant that replicates selectively in p53-deficient human tumor cells”, Science, 274:373-376, 1996 49. Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD, Kirn DH, “ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents [see comments]”, Nat Med, 3:639-645, 1996 50. Heise CC, Williams AM, Xue S, Propst M, Kirn DH, “Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy”, Cancer Research, 59: 2623-2628, 1999 51. Rogulski KR, Freytag SO, Zhang K, Gilbert JD, Paielli DL, Kim JH, Heise CC, Kirn DH, “In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy”, Cancer Research, 60:1193-1196, 2000 52. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B, Gillenwater AM, Bruso P, Kaye SB, Hong WK, Kirn DH, “A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer”, Nature Med, 6:879-885, 2000 53. Lamont JP, Nemunaitis J, Kuhn JA, Landers SA, McCarty TM, “A prospective phase II trial of ONYX-015 adenovirus and chemotherapy in recurrent squamous cell carcinoma of the head and neck (the Baylor experience)”, Annals of Surgical Oncology, 7: 588-592, 2000 54. Suzuki K, Fueyo J, Krasnykh V, Reynolds P, Curiel DT, Alemany RA, “Conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency”, Clin Cancer Res, 7: 120-126, 2001 55. Cunningham C, NJ, Richards D, Tong A, Zhang Y, Su D, Chada S, Mhashilkar A, Zhou-Yang H, Parker K, Wilson D, Merritt J, Coffee K, “A phase I dose-escalation pharmacokinetic and pharmacodynamic study of INGN 241 (Ad-mda7) in patients with advanced solid tumors”, Proc of ASCO, 21: 23a, 2002 56. Alvarez RD, Curiel DT, “A phase I study of recombinant adenovirus vector-mediated delivery of an anti-erbB-2 single-chain (sFv) antibody gene for previously treated ovarian and extraovarian cancer patients”, Human Gene Therapy, 8: 229-242, 1997 57. Alvarez RD, Barnes MN, Gomez-Navarro J, Wang M, Strong TV, Arafat W, Arani RB, Johnson MR, Roberts BL, Siegal GP, Curiel DT, “A cancer gene therapy approach utilizing an anti-erbB-2 singlechain antibody-encoding adenovirus (AD21): a phase I trial”, Clin Cancer Res, 6: 3081-3087, 2000 58. Buller RE, Shahin MS, Karlan B, Horowitz J, Mahavni V, Patrauskas S, et al., “Multi-dose intraperitoneal Rad/p53 (SCH58500) gene replacement combined with chemotherapy in heavily pretreated recurrent ovarian cancer is asscociated with prolonged survival”, Proc Am Soc Clin Oncol, 20: 262a, 2001 59. Tanaka T, Kanai F, Okabe S, Yoshida Y, Wakimoto H, Hamada H, Shiratori Y, Lan K, Ishitobi M, Omata M, “Adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen-producing human gastric carcinoma cells in vitro”, Cancer Res, 56: 1341-1345, 1996 60. Osaki T, Tanio Y, Tachibana I, Hosoe S, Kumagai T, Kawase I, Oikawa S, Kishimoto T, “Gene therapy for carcinoembryonic antigenproducing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene”, Cancer Res, 54: 5258-5261, 1994 61. Lan KH, Kanai F, Shiratori Y, Ohashi M, Tanaka T, Okudaira T, Yoshida Y, Hamada H, Omata M, “In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma”, Cancer Res, 57: 4279-4284, 1997 62. Brand K, Loser P, Arnold W, Bartels T, Strauss M, “Tumor cellspecific transgene expression prevents liver toxicity of the adeno-HSVtk/GCV approach”, Gene Therapy, 5: 1363-1371, 1998. 91 63. Kanai F, Lan KH, Shiratori Y, Tanaka T, Ohashi M, Okudaira T, Yoshida Y, Wakimoto H, Hamada H, Nakabayashi H, Tamaoki T, Omata M, “In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene”, Cancer Res, 57: 461-465, 1997 64. Chung I, Schwartz PE, Crystal RG, Pizzorno G, Leavitt J, Deisseroth AB, “Use of L-plastin promoter to develop an adenoviral system that confers transgene expression in ovarian cancer cells but not in normal mesothelial cells”, Cancer Gene Therapy, 6: 99-106, 1999 65. Peng XY, Won JH, Rutherford T, Fujii T, Zelterman D, Pizzorno G, Sapi E, Leavitt J, Kacinski B, Crystal R, Schwartz P, Deisseroth A, “The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines”, Cancer Res, 61: 4405-4413, 2001 66. Friedman EL, Hayes DF, Kufe DW, “Reactivity of monoclonal antibody DF3 with a high molecular weight antigen expressed in human ovarian carcinomas”, Cancer Res, 46: 5189-5194, 1986 67. Tai YT, Strobel T, Kufe D, Cannistra SA, “In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene”, Cancer Res, 59: 2121-2126, 1999 68. Casado E, Gomez-Navarro J, Yamamoto M, Adachi Y, Coolidge CJ, Arafat WO, Barker SD, Wang MH, Mahasreshti PJ, Hemminki A, Gonzalez-Baron M, Barnes MN, Pustilnik TB, Siegal GP, Alvarez RD, Curiel DT, “Strategies to accomplish targeted expression of transgenes in ovarian cancer for molecular therapeutic applications”, Clin Cancer Res, 7: 2496-2504, 2001 69. Abe T, Tominaga Y, Kikuchi T, Watanabe A, Satoh K, Watanabe Y, Nukiwa T, “Bacterial pneumonia causes augmented expression of the secretory leukoprotease inhibitor gene in the murine lung”, Am J Respir Crit Care Med, 156: 1235-1240, 1997 70. Barker SD, Kanerva A, Rivera A, Coolidge C, Yamamoto M, Hakkarainen T, Alvarez RD, Curiel DT, Hemminki A, “The reulatory sequences of the secretory leukoprotease inhibitor gene as a promising tissue-specific promoter for ovarian cancer gene therapy”, Mol Ther, 5: S412, 2002 71. Siders WM, Halloran PJ, Fenton RG, “Transcriptional targeting of recombinant adenoviruses to human and murine melanoma cells”, Cancer Res, 56: 5638-5646, 1996 72. Ring CJ, Harris JD, Hurst HC, Lemoine NR, “Suicide gene expression induced in tumour cells transduced with recombinant adenoviral, 92 retroviral and plasmid vectors containing the ERBB2 promoter”, Gene Ther, 3: 1094-1103, 1996 73. Strayer MS, Guttentag SH, Ballard PL, “Targeting type II and Clara cells for adenovirus-mediated gene transfer using the surfactant protein B promoter”, Am J Respir Cell Mol Biol, 18: 1-11, 1998 74. Lee EJ, Martinson F, Kotlar T, Thimmapaya B, Jameson JL, “Adenovirus-mediated targeted expression of toxic genes to adrenocorticotropin-producing pituitary tumors using the proopiomelanocortin promoter”, J Clin Endocrinol Metab, 86: 3400-3409, 2001 75. Nettelbeck DM, Jerome V, Muller R, “Gene therapy: designer promoters for tumour targeting”, Trends Genet, 16: 174-181, 2000 76. Walton T, Wang JL, Ribas A, Barsky SH, Economou J, Nguyen M, “Endothelium-specific expression of an E-selectin promoter recombinant adenoviral vector”, Anticancer Res, 18: 1357-1360, 1998 77. Varda-Bloom N, Shaish A, Gonen A, Levanon K, Greenbereger S, Ferber S, Levkovitz H, Castel D, Goldberg I, Afek A, Kopolovitc Y, Harats D, “Tissue-specific gene therapy directed to tumor angiogenesis”, Gene Ther, 8: 819-827, 2001 78. Katabi MM, Chan HL, Karp SE, Batist G, “Hexokinase type II: a novel tumor-specific promoter for gene-targeted therapy differentially expressed and regulated in human cancer cells”, Human Gene Therapy, 10: 155-164, 1999 79. Manome Y, Kunieda T, Wen PY, Koga T, Kufe DW, Ohno T, “Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iododeoxyuridine”, Hum Gene Ther, 9: 1409- 1417, 1998 80. Rein DT, Breidenbach M, Bauerschmitz GJ, Herrmann I, Bender HG, Dall P, „Steuerung einer Krebsgentherapie über strahleninduzierbare Promotoren. Ein neuer Ansatz zur kombinierten Radiochemo- und Gentherapie des Zervixkarzinoms [Radiation-induced Promoters for Combined Radiochemo and Gene Therapie of Zervical Carcinoma]“, In: Abstraktband der 204. Tagung der NWGGG 2005, Düsseldorf/Germany 2005 81. Dmitriev I, Krasnykh V, Miller CR, Wang M, Kashentseva E, Mikheeva G, Belousova N, Curiel DT, „An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism“, J Virol, 72: 9706-9713, 1998 82. Krasnykh V, Dmitriev I, Mikheeva G, Miller CR, Belousova N, Curiel DT, “Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob”, Journal of Virology, 72: 1844-1852, 1998 83. Hemminki A, Belousova N, Zinn KR, Liu B, Wang M, Chaudhuri TR, Rogers BE, Buchsbaum DJ, Siegal GP, Barnes MN, Gomez- Navarro J, Curiel DT, Alvarez RD, “An adenovirus with enhanced infectivity mediates molecular chemotherapy of ovarian cancer cells and allows imaging of gene expression”, Mol Ther, 4: 223-231, 2001 84. Hemminki A, Zinn KR, Liu B, Chaudhuri TR, Desmond RA, Rogers BE, Barnes MN, Alvarez RD, Curiel DT, “In Vivo Molecular Chemotherapy and Noninvasive Imaging With an Infectivity-Enhanced Adenovirus”, J Natl Cancer Inst, 94: 741-749, 2002 85. U.S. Department of Health and Human Services, National Institutes of Health, Recombinant DNA Advisory Committee: minutes of meeting, December 13 & 15, 2000. Hum Gene Ther, 12: 1559-1584, 2001 86. Hemminki A, Alvarez RD, “Adenoviruses in oncology: a viable option?”, BioDrugs, 16: 77-87, 2002 87. Lieber A, He CY, Meuse L, Schowalter D, Kirillova I, Winther B, Kay MA, “The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors”, J Virol, 71: 8798-8807, 1997 88. Einfeld DA, Schroeder R, Roelvink PW, Lizonova A, King CR, Kovesdi I, Wickham TJ, “Reducing the native tropism of adenovirus vectors requires removal of both CAR and integrin interactions”, J Virol, 75: 11284-11291, 2001 89. Bayo-Puxan N, Cascallo M, Gros A, Huch M, Fillat C, Alemany R, “Role of the putative heparan sulfate glycosaminoglycan-binding site of the adenovirus type 5 fiber shaft on liver detargeting and knob-mediated retargeting”, J Gen Virol, 87: 2487-2495, 2006 90. Kanerva A, Zinn KR, Chaudhuri TR, Lam JT, Suzuki K, Uil TG, Hakkarainen T, Bauerschmitz GJ, Wang M, Liu B, Cao Z, Alvarez RD, Curiel DT, Hemminki A, “Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus”, Mol Ther, 8: 449-458, 2003 91. Raki M, Kanerva A, Ristimaki A, Desmond RA, Chen DT, Ranki T, Sarkioja M, Kangasniemi L, Hemminki A, “Combination of gemcitabine and Ad5/3-Delta24, a tropism modified conditionally replicating adenovirus, for the treatment of ovarian cancer”, Gene Ther, 12: 1198-1205, 2005 92. Von Seggern DJ, Huang S, Fleck SK, Stevenson SC, Nemerow GR, “Adenovirus vector pseudotyping in fiber-expressing cell lines: improved transduction of Epstein-Barr virus-transformed B cells”, J Virol, 74: 354-362, 2000 93. Krasnykh VN, Mikheeva GV, Douglas JT, Curiel DT, “Generation of recombinant adenovirus vectors with modified fibers for altering viral tropism”, Journal of Virology, 70: 6839-6846, 1996 94. Sirena D, Lilienfeld B, Eisenhut M, Kalin S, Boucke K, Beerli RR, Vogt L, Ruedl C, Bachmann MF, Greber UF, Hemmi S, “The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3”, J Virol, 78: 4454-4462, 2004 95. Marttila M, Persson D, Gustafsson D, Liszewski MK, Atkinson JP, Wadell G, Arnberg N, “CD46 is a cellular receptor for all species B adenoviruses except types 3 and 7”, J Virol, 79: 14429-14436, 2005 96. Tuve S, Wang H, Ware C, Liu Y, Gaggar A, Bernt K, Shayakhmetov D, Li Z, Strauss R, Stone D, Lieber A, “A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells”, J Virol, 2006 97. Kangasniemi L, Kiviluoto T, Kanerva A, Raki M, Ranki T, Sarkioja M, Wu H, Marini F, Hockerstedt K, Isoniemi H, Alfthan H, Stenman UH, Curiel DT, Hemminki A, “Infectivity-enhanced adenoviruses deliver efficacy in clinical samples and orthotopic models of disseminated gastric cancer”, Clin Cancer Res, 12: 3137-3144, 2006 98. Ranki T, Kanerva A, Ristimaki A, Hakkarainen T, Sarkioja M, Kangasniemi L, Raki M, Laakkonen P, Goodison S, Hemminki AA, “Heparan sulfate-targeted conditionally replicative adenovirus, Ad5.pk7- Delta24, for the treatment of advanced breast cancer”, Gene Ther, 2006 99. Sarkioja M, Kanerva A, Salo J, Kangasniemi L, Eriksson M, Raki M, Ranki T, Hakkarainen T, Hemminki A, “Noninvasive imaging for evaluation of the systemic delivery of capsid-modified adenoviruses in an orthotopic model of advanced lung cancer”, Cancer, 107: 1578-1588, 2006 100. Rancourt C, Rogers BE, Sosnowski BA, Wang M, Piche A, Pierce GF, Alvarez RD, Siegal GP, Douglas JT, Curiel DT, “Basic 94 fibroblast growth factor enhancement of adenovirus-mediated delivery of the herpes simplex virus thymidine kinase gene results in augmented therapeutic benefit in a murine model of ovarian cancer”, Clin Cancer Res, 4: 2455-2461, 1998 101. Gu DL, Gonzalez AM, Printz MA, Doukas J, Ying W, D'Andrea M, Hoganson DK, Curiel DT, Douglas JT, Sosnowski BA, Baird A, Aukerman SL, Pierce GF, “Fibroblast growth factor 2 retargeted adenovirus has redirected cellular tropism: evidence for reduced toxicity and enhanced antitumor activity in mice”, Cancer Res, 59: 2608-2614, 1999 102. Wesseling JG, Bosma PJ, Krasnykh V, Kashentseva EA, Blackwell JL, Reynolds PN, Li H, Parameshwar M, Vickers SM, Jaffee EM, Huibregtse K, Curiel DT, Dmitriev I, “Improved gene transfer efficiency to primary and established human pancreatic carcinoma target cells via epidermal growth factor receptor and integrin-targeted adenoviral vectors”, Gene Ther, 8: 969-976., 2001 103. Kashentseva EA, Seki T, Curiel DT, Dimitriev IP, “Adenovirus targeting to c-erbB-2 oncoprotein by single-chain antibody fused to trimeric form of adenovirus receptor ectodomain”, Cancer Res, 62: 609-616, 2002 104. Hemminki A, Dimitriev I, Liu B, Desmond RA, Alemany R, Curiel DT, “Targeting oncolytic adenoviral agents to the epidermal growth factor pathway with a secretory fusion molecule”, Cancer Res, 61: 6377-6381, 2001 105. Glasgow JN, Bauerschmitz GJ, Curiel DT, Hemminki A, “Transductional and transcriptional targeting of adenovirus for clinical applications”, Curr Gene Ther, 4: 1-14, 2004 106. Heise C, Hermiston T, Johnson L, Brooks G, Sampson-Johannes A, Williams A, Hawkins L, Kirn D, “An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy”, Nature Med, 6: 1134-1139, 2000 107. Balague C, Noya F, Alemany R, Chow LT, Curiel DT, “Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes”, J Virol, 75: 7602-7611, 2001 108. Lam JT, Kanerva A, Bauerschmitz GJ, Takayama K, Suzuki K, Yamamoto M, Bhoola SM, Liu B, Wang M, Barnes MN, Alvarez R, Siegal GP, Curiel DT, Hemminki A, “Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy”, J Gene Med, 6: 1333-1342, 2004 109. Curiel DT, “The development of conditionally replicative adenoviruses for cancer therapy”, Clin Cancer Res, 6: 3395-3399, 2000 110. Curiel DT, “Rational design of viral vectors based on rigorous analysis of capsid structures [comment]. Molecular Therapy: the Journal of the American Society of Gene Therapy”, 1: 3-4, 2000 111. Gomez-Navarro J, Curiel DT, “Conditionally replicative adenoviral vectors for cancer gene therapy”, Lancet Oncol, 1: 148-158, 2000 112. Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP, “A mutant 75 oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo”, Oncogene, 19: 2-12, 2000 113. Nettelbeck DM, Rivera AA, Balague C, Alemany R, Curiel DT, “Novel Oncolytic Adenoviruses Targeted to Melanoma: Specific Viral Replication and Cytolysis by Expression of E1A Mutants from the Tyrosinase Enhancer/Promoter”, Cancer Res, 62: 4663-4670, 2002 114. Takayama K, Reynolds PN, Adachi Y, Kaliberova L, Uchino J, Nakanishi Y, Curiel DT, “Vascular endothelial growth factor promoterbased conditionally replicative adenoviruses for pan-carcinoma application”, Cancer Gene Ther, 2006 115. Zhu ZB, Chen Y, Makhija SK, Lu B, Wang M, Rivera AA, Yamamoto M, Wang S, Siegal GP, Curiel DT, McDonald JM, “Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma”, Int J Oncol, 29: 1319-1329, 2006 116. Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR, “Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells”, Cancer Res, 57: 2559-2563, 1997 117. Yu DC, Sakamoto GT, Henderson DR, “Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy”, Cancer Research, 59: 1498-1504, 1999 118. Hallenbeck PL, Chang YN, Hay C, Golightly D, Stewart D, Lin J, Phipps S, Chiang YL, “A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma”, Hum Gene Ther, 10: 1721-1733, 1999 119. Kurihara T, Brough DE, Kovesdi I, Kufe DW, “Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen”, J Clin Invest, 106: 763-771, 2000 120. Hernandez-Alcoceba R, Pihalja M, Wicha MS, Clarke MF, “A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors”, Hum Gene Ther, 11: 2009-2024, 2000 121. Adachi Y, Reynolds PN, Yamamoto M, Wang M, Takayama K, Matsubara S, Muramatsu T, Curiel DT, “A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging”, Cancer Res, 61: 7882-7888, 2001 122. Freytag SO, Rogulski KR, Paielli DL, Gilbert JD, Kim JH, “A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy”, Human Gene Therapy, 9: 1323-1333, 1998 123. Wildner O, Morris JC, Vahanian NN, Ford H, Jay W, Ramsey WJ, Blaese RM, “Adenoviral vectors capable of replication improve the efficacy of HSVtk/GCV suicide gene therapy of cancer”, Gene Ther, 6: 57-62, 1999 124. McCormick F, “Cancer-specific viruses and the development of ONYX-015”, Cancer Biol Ther, 2: S157-160, 2003 125. Cohen EE, Rudin CM, “ONYX-015. Onyx Pharmaceuticals”, Curr Opin Investig Drugs, 2: 1770-1775, 2001 126. Wadler S, Yu B, Tan JY, Kaleya R, Rozenblit A, Makower D, Edelman M, Lane M, Hyjek E, Horwitz M, “Persistent replication of the modified chimeric adenovirus ONYX-015 in both tumor and stromal cells from a patient with gall bladder carcinoma implants”, Clin Cancer Res, 9: 33-43, 2003 127. Edwards SJ, Dix BR, Myers CJ, Dobson-Le D, Huschtscha L, Hibma M, Royds J, Braithwaite AW, “Evidence that replication of the antitumor adenovirus ONYX-015 is not controlled by the p53 and p14(ARF) tumor suppressor genes”, J Virol, 76: 12483-12490, 2002 128. Macrae M, Neve RM, Rodriguez-Viciana P, Haqq C, Yeh J, Chen C, Gray JW, McCormick FA, “Conditional feedback loop regulates Ras activity through EphA2”, Cancer Cell, 8: 111-118, 2005 129. Rothmann T, Hengstermann A, Whitaker NJ, Scheffner M, zur Hausen H, “Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells”, Journal of Virology, 72: 9470-9478, 1998 130. Hay JG, Shapiro N, Sauthoff H, Heitner S, Phupakdi W, Rom WN, “Targeting the replication of adenoviral gene therapy vectors to lung cancer cells: the importance of the adenoviral E1b-55kD gene”, Hum Gene Ther, 10: 579-590, 1999 131. Dix BR, Edwards SJ, Braithwaite AW, “Does the Antitumor Adenovirus ONYX-015/dl1520 Selectively Target Cells Defective in the p53 Pathway?”, J Virol, 75: 5443-5447., 2001 132. Barker DD, Berk AJ, “Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection”, [published erratum appears in Virology 1987 May;158(1):263]. Virology, 156: 107-121, 1987 133. Sherr CJ, “Cancer cell cycles”, Science, 274: 1672-1677., 1996 134. Doronin K, Toth K, Kuppuswamy M, Ward P, Tollefson AE, Wold WS, “Tumor-specific, replication-competent adenovirus vectors overexpressing the adenovirus death protein”, J Virol, 74: 6147-6155, 2000 135. Doronin K, Kuppuswamy M, Toth K, Tollefson AE, Krajcsi P, Krougliak V, Wold WS, “Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy”, J Virol, 75: 3314-3324, 2001 136. Douglas JT, Kim M, Sumerel LA, Carey DE, Curiel DT, “Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically dependent on tumor expression of primary ad receptors”, Cancer Res, 61: 813-817, 2001 137. Shinoura N, Yoshida Y, Tsunoda R, Ohashi M, Zhang W, Asai A, Kirino T, Hamada H, “Highly augmented cytopathic effect of a fibermutant E1B-defective adenovirus for gene therapy of gliomas”, Cancer Res, 59: 3411-3416, 1999 138. Lamfers ML, Grill J, Dirven CM, van Beusechem VW, Geoerger B, van den Berg J, Alemany R, Fueyo J, Curiel DT, Vassal G, Pinedo HM, Vandertop WP, Gerritsen WR, “Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy”, Cancer Res, 62: 5736-5742, 2002 139. Bauerschmitz GJ, Lam JT, Kanerva A, Suzuki K, Nettelbeck DM, Dmitriev I, Krasnykh V, Mikheeva GV, Barnes MN, Alvarez RD, Dall P, Alemany R, Curiel DT, Hemminki A, “Treatment of ovarian cancer 72 with a tropism modified oncolytic adenovirus”, Cancer Res, 62: 1266-1270, 2002 140. Kanerva A, Hemminki A, “Adenoviruses for treatment of cancer”, Ann Med, 37: 33-43, 2005 141. Breidenbach M, Rein DT, Wang M, Nettelbeck DM, Hemminki A, Ulasov I, Rivera A, Everts M, Alvarez RD, Douglas JT, Curiel DT, “Genetic replacement of the adenovirus shaft fiber reduces liver tropism in ovarian cancer gene therapy”, Hum Gene Ther, 15: 509-518, 2004 142. Stecher H, Shayakhmetov DM, Stamatoyannopoulos G, Lieber AA, “Capsid-modified adenovirus vector devoid of all viral genes: assessment of transduction and toxicity in human hematopoietic cells”, Mol Ther, 4: 36-44, 2001 143. Yu L, Takenobu H, Shimozato O, Kawamura K, Nimura Y, Seki N, Uzawa K, Tanzawa H, Shimada H, Ochiai T, Tagawa M, “Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells”, Oncol Rep, 14: 831-835, 2005 144. Ni S, Gaggar A, Di Paolo N, Li ZY, Liu Y, Strauss R, Sova P, Morihara J, Feng O, Kiviat N, Toure P, Sow PS, Lieber A Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting. Cancer Gene Ther, 13: 1072-1081, 2006. 145. DiPaolo N, Ni S, Gaggar, A, Strauss R, Tuve S, Li ZY, Stone D, Shayakhmetov D, Kiviat N, Toure P, Sow S, Horvat B, Lieber A, “Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination”, Mol Ther, 13: 756-765, 2006 146. Stone D, Lieber A, “New serotypes of adenoviral vectors”, Curr Opin Mol Ther, 8: 423-431, 2006 147. Smith BF, Curiel DT, Ternovoi VV, Borovjagin AV, Baker HJ, Cox N, Siegal GP, „Administration of a conditionally replicative oncolytic canine adenovirus in normal dogs“, Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA, Cancer Biother Radiopharm Dec., 21(6):601-6, 2006 148. Smith RR, Huebner RJ, Rowe WP, Schatten WE, Thomas LB, “Studies on the use of viruses in the treatment of carcinoma of the cervix”, Cancer, 9: 1211-1218, 1956 149. Ganly I, Eckhardt SG, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C, von Hoff DD, Kaye SB, “A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer”, [published erratum appears in Clin Cancer Res 2000 May;6(5):2120]. Clin Cancer Res, 6: 798-806, 2000 150. Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T, Kaye S, Kirn D, “Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial”, Cancer Res, 60: 6359-6366, 2000 151. Xia ZJ, Chang JH, Zhang L, Jiang WQ, Guan ZZ, Liu JW, Zhang Y, Hu XH, Wu GH, Wang HQ, Chen ZC, Chen JC, Zhou QH, Lu JW, Fan QX, Huang JJ, Zheng X, “[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus.]”, Ai Zheng, 23: 1666-1670, 2004 152. Casado E, Alemany R, Suzuki K, Gomez Navarro J, Arafat W, Barker S, De Castro J, Feliu J, Zamora P, Lopez J, Gonzalez Baron M, Curiel DT, “A Conditionally Replicative Adenovirus with Enhanced Infectivity (Ad D24-RGD) for Ovarian Cancer Gene Therapy: Preclinical Evaluation of Selectivity, Oncolytic Potency and Chemotherapy Combination Strategies”, Proceedings of the American Society of Clinical Oncology, 20: 253a, 2001 153. Lam JT, Kanerva A, Bauerschmitz GJ, Barker SD, Straughn MJ, Wang M, Blackwell JL, Alvarez RD, Curiel DT, Hemminki A, “Spheroids as a Three Dimensional Model For Analysis of Replicative Viral Agents on Primary Tumor Cells”, Mol Ther, 3: S87, 2001 154. van Beusechem VW, Mastenbroek DC, van den Doel PB, Lamfers ML, Grill J, Wurdinger T, Haisma HJ, Pinedo HM, Gerritsen WR, “Conditionally replicative adenovirus expressing a targeting adapter molecule exhibits enhanced oncolytic potency on CAR-deficient tumors”, Gene Ther, 10: 1982-1991, 2003 155. Rein DT, Breidenbach M, Kirby TO, Han T, Siegal GP, Bauerschmitz GJ, Wang M, Nettelbeck DM, Tsuruta Y, Yamamoto M, Dall P, Hemminki A, Curiel DT, “A fiber-modified, secretory leukoprotease inhibitor promoter-based conditionally replicating adenovirus for treatment of ovarian cancer”, Clin Cancer Res, 11: 1327-1335, 2005 156. Vattemi E, Claudio PP, “Adenoviral gene therapy in head and neck cancer”, Drug News Perspect, 19: 329-337, 2006 157. Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M, Hurskainen H, Tyynela K, Turunen M, Vanninen R, Lehtolainen P, Paljarvi L, Johansson R, Vapalahti M, Yla-Herttuala S, “Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses”, Hum Gene Ther, 11: 2197-2205, 2000 158. Immonen A, Vapalahti M, Tyynela K, Hurskainen H, Sandmair A, Vanninen R, Langford G, Murray N, Yla-Herttuala S, “AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study”, Mol Ther, 10: 967-972, 2004 159. Schuler M, Herrmann R, De Greve JL, Stewart AK, Gatzemeier U, Stewart DJ, Laufman L, Gralla R, Kuball J, Buhl R, Heussel CP, Kommoss F, Perruchoud AP, Shepherd FA, Fritz MA, Horowitz JA, Huber C, Rochlitz C, “Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: Results of a multicenter phase II study”, J Clin Oncol, 19: 1750-1758, 2001 160. Peng Z, “Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers”, Hum Gene Ther, 16: 1016-1027, 2005 161. Bauerschmitz GJ, Kanerva A, Wang M, Herrmann I, Shaw DR, Strong TV, Desmond R, Rein DT, Dall P, Curiel DT, Hemminki A, “Evaluation of a selectively oncolytic adenovirus for local and systemic treatment of cervical cancer”, Int J Cancer, 111: 303-309, 2004 162. Kanerva A, Raki M, Ranki T, Särkioja M, Koponen J, Desmond RA, Helin A, Stenman UH, Isoniemi H, Höckerstedt K, Ristimäki A, Hemminki A, “Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity.“, J Gene Med; 9(1):3-9, Jan 2007 163. Pesonen S, Diaconu I, Cerullo V, Escutenaire S, Raki M, Kangasniemi L, Nokisalmi P, Dotti G, Guse K, Laasonen L, Partanen K, Karli E, Haavisto E, Oksanen M, Karioja-Kallio A, Hannuksela P, Holm SL, Kauppinen S, Joensuu T, Kanerva A, Hemminki A, “Integrin targeted oncolytic adenoviruses Ad5-D24-RGD and Ad5-RGD-D24-GMCSF for treatment of patients with advanced chemotherapy refractory solid tumors.”, Int J Cancer, Apr 15;130(8):1937-47. doi: 10.1002/ijc.26216, 2012 | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 12/2006 bis 01/2015 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 01.06.2015 | |||||||
| Dateien geändert am: | 01.06.2015 | |||||||
| Promotionsantrag am: | 25.07.2014 | |||||||
| Datum der Promotion: | 20.01.2015 |
