Oncolytic adenoviral mutants with E1B19KGene deletions enhance gemcitabine-induced apoptosis in pancreatic carcinoma cells and anti-tumor efficacy in vivo

Clinical Cancer Research

Volumn 15, Issue 5, 2009, Pages 1730-1740

  Leitner, Stephan ^a   Sweeney, Katrina ^a   Öberg, Daniel ^a   Davies, Derek ^b   Miranda, Enrique ^a   Lemoine, Nick R ^a   Halldén, Gunnel ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CYCLIN E; E1A PROTEIN; E1B19K PROTEIN; E3B PROTEIN; GEMCITABINE; MUTANT PROTEIN; ONCOLYTIC ADENOVIRUS; PROTEIN TYROSINE PHOSPHATASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CELL CULTURE; CANCER CELL DESTRUCTION; CELL CYCLE G1 PHASE; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CELL DEATH; CELL MEMBRANE; CELL VIABILITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; DRUG POTENTIATION; DRUG TARGETING; ENZYME ACTIVATION; EXPERIMENTAL NEOPLASM; FRAGMENTATION REACTION; GENE DELETION; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VIVO STUDY; MITOCHONDRION; MOUSE; NONHUMAN; PANCREAS CARCINOMA; PRIORITY JOURNAL; TUMOR XENOGRAFT; VIRAL GENE THERAPY; VIRUS GENE; VIRUS INHIBITION; VIRUS MUTANT;

ADENOCARCINOMA; ADENOVIRIDAE; ADENOVIRUS E1B PROTEINS; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; COMBINED MODALITY THERAPY; DEOXYCYTIDINE; DRUG SYNERGISM; FLOW CYTOMETRY; GENE DELETION; GENE THERAPY; GENETIC VECTORS; HUMANS; IMMUNOBLOTTING; MICE; MICE, INBRED C57BL; MICE, NUDE; MUTATION; ONCOLYTIC VIRUSES; PANCREATIC NEOPLASMS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; S PHASE; VIRUS REPLICATION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 63449117086     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-08-2008     Document Type: Article

References (45)

1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30.
2. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007; 297:267-77.
3. Kasuya H,Takeda S, Nomoto S, Nakao A. The potential of oncolytic virus therapy for pancreatic cancer. Cancer Gene Ther 2005;12:725-36.
4. Harada JN, Berk AJ. p53-Independent and -dependent requirements for E1B-55K in adenovirus type 5 replication. J Virol 1999;73:5333-44.
5. O'Shea CC, Johnson L, Bagus B, et al. Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell 2004;6: 611-23.
6. Khuri FR, Nemunaitis J, Ganly I, et al. 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. Nat Med 2000;6:879-85.
7. Xia ZJ, Chang JH, Zhang L, et al. [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 2004;23: 1666-70.
8. Mulvihill S, Warren R,Venook A, et al. Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial. Gene Ther 2001;8:308-15.
9. Hecht JR, Bedford R, Abbruzzese JL, et al. A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res 2003;9:555-61.
10. Heise C, Hermiston T, Johnson L, et al. An adenovirus E1A mutant that demonstrates potent and selective systemicanti-tumoral efficacy. Nat Med 2000;6: 1134-9.
11. Stolarek R, Gomez-Manzano C, Jiang H, Suttle G, Lemoine MG, Fueyo J. Robust infectivity and replication of A-24 adenovirus induce cell death in human medulloblastoma. Cancer Gene Ther 2004;11: 713-20.
12. Small EJ, Carducci MA, Burke JM, et al. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol Ther 2006;14:107-17.
13. DeWeese TL, van der Poel H, Li S, et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res 2001;61:7464-72.
14. Johnson L, Shen A, Boyle L, et al. Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents. Cancer Cell 2002;1:325-37.
15. Schepelmann S, Hallenbeck P, Ogilvie LM, et al. Systemicgene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2. Cancer Res 2005; 65:5003-8.
16. Liu TC, Hallden G, Wang Y, et al. An E1B-19 kDa gene deletion mutant adenovirus demonstrates tumor necrosis factor-enhanced cancer selectivity and enhanced oncolytic potency. Mol Ther 2004;9: 786-803.
17. Sauthoff H, Heitner S, Rom WN, Hay JG. Deletion of the adenoviral E1b-19kD gene enhances tumor cell killing of a replicating adenoviral vector. Hum Gene Ther 2000;11:379-88.
18. Yoon AR,Kim JH,LeeYS,et al. Markedly enhanced cytolysis by E1B -19kD-deleted oncolytic adenovirus in combination with cisplatin. Hum Gene Ther 2006; 17:379-90.
19. White E Regulation of the cell cycle and apoptosis by the oncogenes of adenovirus. Oncogene 2001;20: 7836-46.
20. Subramanian T, Vijayalingam S, Chinnadurai G. Genetic identification of adenovirus type 5 genes that influence viral spread. J Virol 2006;80:2000-12.
21. Putzer BM, StieweT, Parssanedjad K, Rega S, Esche H. E1A is sufficient by itself to induce apoptosis independent of p53 and other adenoviral gene products. Cell Death Differ 2000;7:177-88.
22. Lomonosova E, Subramanian T, Chinnadurai G. Mitochondrial localization of p53 during adenovirus infection and regulation of its activity by E1B-19K. Oncogene 2005;24:6796-808.
23. Cross JR, Postigo A, Blight K, Downward J. Viral pro-survival proteins block separate stages in Bax activation but changes in mitochondrial ultrastructure still occur. Cell Death Differ 2008;15:997-1008.
24. Liu TC, Wang Y, Hallden G, et al. Functional interactions of antiapoptotic proteins and tumor necrosis factor in the context of a replication-competent adenovirus. Gene Ther 2005;12:1333-46.
25. Harrison D, Sauthoff H, Heitner S, JagirdarJ, Rom WN, Hay JG. Wild-type adenovirus decreases tumor xenograft growth, but despite viral persistence complete tumor responses are rarely achieved - deletion of the viral E1b-19-kD gene increases the viral oncolytic effect. Hum Gene Ther 2001;12:1323-32.
26. Wang Y, Hallden G, Hill R, et al. E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models. Nat Biotechnol 2003;21: 1328-35.
27. Heinemann V, Schulz L, Issels RD, Plunkett W. Gemcitabine: a modulator of intracellular nucleotide and deoxynucleotide metabolism. Semin Oncol 1995;22: 11-8.
28. Chartier C, Degryse E, Gantzer M, Dieterle A, Pavirani A, Mehtali M. Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J Virol 1996;70:4805-10.
29. Cheong SC, Wang Y, Meng JH, et al. E1A-expressing adenoviral E3B mutants act synergistically with chemotherapeutics in immunocompetent tumor models. Cancer Gene Ther 2008;15:40-50.
30. Raki M, Kanerva A, Ristimaki A, et al. Combination of gemcitabine and Ad5/3-Δ24, a tropism modified conditionally replicating adenovirus, for the treatment of ovarian cancer. GeneTher 2005;12:1198-205.
31. Watanabe I, Kasuya H, Nomura N, et al. Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer. Cancer Chemother Pharmacol 2008;61:875-82.
32. Eisenberg DP, Adusumilli PS, Hendershott KJ, et al. 5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer. J Gastrointest Surg 2005;9: 1068-77; discussion 77-9.
33. Toth K, Spencer JF, Dhar D, et al. Hexadecyloxy-propyl-cidofovir, CMX001, prevents adenovirus- induced mortality in a permissive, immunosuppressed animal model. Proc Natl Acad Sci U S A 2008;105: 7293-7.
34. Cappella P, Tomasoni D, Faretta M, et al. Cell cycle effects of gemcitabine. Int J Cancer 2001;93:401-8.
35. Spitkovsky D, Jansen-Durr P, Karsenti E, Hoffman I. S-phase induction by adenovirus E1A requires activation of cdc25a tyrosine phosphatase. Oncogene 1996;12:2549-54.
36. Bonapace IM, Latella L, Papait R, et al. Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. J Cell Biol 2002;157:909-14.
37. Abou El Hassan MA, van der Meulen-Muileman I, Abbas S, Kruyt FA. Conditionally replicating adenoviruses kill tumor cells via a basic apoptotic machinery-independent mechanism that resembles necrosis-like programmed cell death. J Virol 2004;78:12243-51.
38. Baird SK, Aerts JL, Eddaoudi A, Lockley M, Lemoine NR, McNeish IA. Oncolytic adenoviral mutants induce a novel mode of programmed cell death in ovarian cancer. Oncogene 2008;27:3081 -90.
39. Chattopadhyay D, Ghosh MK, Mal A, Harter ML. Inactivation of p21 by E1A leads to the induction of apoptosis in DNA-damaged cells. J Virol 2001;75: 9844-56.
40. Yu D, Wolf JK, Scanlon M, Price JE, Hung MC. Enhanced c-erbB-2/neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res 1993;53:891-8.
41. Ueno NT, Bartholomeusz C, Herrmann JL, et al. E1A-mediated paclitaxel sensitization in HER-2/neu-overexpressing ovarian cancer SKOV3.ip1 through apoptosis involving the caspase-3 pathway. Clin Cancer Res 2000;6:250-9.
42. Zhou Z, Jia SF, Hung MC, Kleinerman ES. E1A sensitizes HER2/neu-overexpressing Ewing's sarcoma cells to topoisomerase II-targeting anticancer drugs. Cancer Res 2001;61:3394-8.
43. Lee WP, Tai DI, Tsai SL, et al. Adenovirus type 5 E1A sensitizes hepatocellular carcinoma cells to gemcitabine. Cancer Res 2003;63:6229-36.
44. Rao XM, Tseng MT, Zheng X, et al. E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells. Cancer Gene Ther 2004;11:585-93.
45. Hu B, Zhu H, Qiu S, et al. Enhanced TRAIL sensitivity by E1A expression in human cancer and normal cell lines: inhibition by adenovirus E1B19K and E3 proteins. Biochem Biophys Res Commun 2004;325:1153-62.