Journal Mobile Options
Table of Contents
Vol. 97, No. 1, 2013
Issue release date: February 2013
Section title: Genetic Mechanisms
Neuroendocrinology 2013;97:26–34
(DOI:10.1159/000336084)

Virotherapy of Neuroendocrine Tumors

Essand M.
Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Do you have an account?

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger (new!)
  • Unrestricted printing, no saving restrictions for personal use
  • Reduced rates with a PPV account
read more

Direct: USD 38.00
Account: USD 26.50

Select

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restriction apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Automatic perpetual access to all articles of the subscribed year(s)
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select


Article / Publication Details

First-Page Preview
Abstract of Genetic Mechanisms

Received: 6/14/2011 1:18:07 PM
Accepted: 12/11/2011
Published online: 2/29/2012

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 1

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

Most patients with small intestinal neuroendocrine tumors (SI-NETs), also referred to as midgut carcinoids, present with systemic disease at the time of diagnosis with metastases primarily found in regional lymph nodes and the liver. Curative treatment is not available for these patients and there is a need for novel and specific therapies. Engineered oncolytic viruses may meet the need and play an important role in the future management of SI-NET liver metastases. This review focuses on adenovirus as the oncolytic anti-cancer agent and its potential curative role for SI-NET liver metastases, but it also summarizes the use of oncolytic viruses for NETs in general. It discusses how specific features of neuroendocrine cell biology can be used to engineer viruses to become selective for infection of NET cells and/or replication within NET cells. In addition, it points out the advantages and shortcomings of using replicating viruses in the treatment of cancer and addresses research fields that can increase the efficacy of virus-based therapy.


Article / Publication Details

First-Page Preview
Abstract of Genetic Mechanisms

Received: 6/14/2011 1:18:07 PM
Accepted: 12/11/2011
Published online: 2/29/2012

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 1

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. McCormick F: Future prospects for oncolytic therapy. Oncogene 2005;24:7817–7819.
  2. Cattaneo R, Miest T, Shashkova EV, Barry MA: Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol 2008;6:529–540.
  3. Ribacka C, Hemminki A: Virotherapy as an approach against cancer stem cells. Curr Gene Ther 2008;8:88–96.
  4. Vattemi E, Claudio PP: Adenoviral gene therapy in head and neck cancer. Drug News Perspect 2006;19:329–337.
  5. Young LS, Searle PF, Onion D, Mautner V: Viral gene therapy strategies: from basic science to clinical application. J Pathol 2006;208:299–318.
  6. Kuster K, Koschel A, Rohwer N, Fischer A, Wiedenmann B, Anders M: Downregulation of the coxsackie and adenovirus receptor in cancer cells by hypoxia depends on HIF-1α. Cancer Gene Ther 2010;17:141–146.
  7. Shayakhmetov DM, Papayannopoulou T, Stamatoyannopoulos G, Lieber A: Efficient gene transfer into human CD34+ cells by a retargeted adenovirus vector. J Virol 2000;74:2567–2583.
  8. Krasnykh VN, Mikheeva GV, Douglas JT, Curiel DT: Generation of recombinant adenovirus vectors with modified fibers for altering viral tropism. J Virol 1996;70:6839–6846.
  9. Wang H, Li ZY, Liu Y, Persson J, Beyer I, Moller T, Koyuncu D, Drescher MR, Strauss R, Zhang XB, Wahl JK 3rd, Urban N, Drescher C, Hemminki A, Fender P, Lieber A: Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med 2011;17:96–104.
  10. Wickham TJ, Tzeng E, Shears LL 2nd, Roelvink PW, Li Y, Lee GM, Brough DE, Lizonova A, Kovesdi I: Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins. J Virol 1997;71:8221–8229.
  11. 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 1998;72:9706–9713.
  12. Kurachi S, Koizumi N, Sakurai F, Kawabata K, Sakurai H, Nakagawa S, Hayakawa T, Mizuguchi H: Characterization of capsid-modified adenovirus vectors containing heterologous peptides in the fiber knob, protein IX, or hexon. Gene Ther 2007;14:266–274.
  13. Piao Y, Jiang H, Alemany R, Krasnykh V, Marini FC, Xu J, Alonso MM, Conrad CA, Aldape KD, Gomez-Manzano C, Fueyo J: Oncolytic adenovirus retargeted to Δ-EGFR induces selective antiglioma activity. Cancer Gene Ther 2009;16:256–265.
  14. Belousova N, Korokhov N, Krendelshchikova V, Simonenko V, Mikheeva G, Triozzi PL, Aldrich WA, Banerjee PT, Gillies SD, Curiel DT, Krasnykh V: Genetically targeted adenovirus vector directed to CD40-expressing cells. J Virol 2003;77:11367–1177.
  15. Kelly EJ, Hadac EM, Greiner S, Russell SJ: Engineering microRNA responsiveness to decrease virus pathogenicity. Nat Med 2008;14:1278–1283.
  16. Cawood R, Chen HH, Carroll F, Bazan- Peregrino M, van Rooijen N, Seymour LW: Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells. PLoS Pathog 2009;5:e1000440.
  17. Ylosmaki E, Hakkarainen T, Hemminki A, Visakorpi T, Andino R, Saksela K: Generation of a conditionally replicating adenovirus based on targeted destruction of E1A mRNA by a cell type-specific MicroRNA. J Virol 2008;82:11009–11015.
  18. 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. Nat Med 2000;6:1134–1139.
  19. Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH, Lloyd R, Vasmatzis G, Demoulin JB, Giandomenico V: Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol 2009;22:261–272.
  20. Vikman S, Essand M, Cunningham JL, de la Torre M, Oberg K, Totterman TH, Giandomenico V: Gene expression in midgut carcinoid tumors: potential targets for immunotherapy. Acta Oncol 2005;44:32–40.
  21. Volante M, Rosas R, Allia E, Granata R, Baragli A, Muccioli G, Papotti M: Somatostatin, cortistatin and their receptors in tumours. Mol Cell Endocrinol 2008;286:219–229.
  22. Leja J, Dzojic H, Gustafson E, Oberg K, Giandomenico V, Essand M: A novel chromogranin-a promoter-driven oncolytic adenovirus for midgut carcinoid therapy. Clin Cancer Res 2007;13:2455–2462.
  23. Leja J, Nilsson B, Yu D, Gustafson E, Akerstrom G, Oberg K, Giandomenico V, Essand M: Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability. PLoS One 2010;5:e8916.
  24. Susini C, Buscail L: Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006;17:1733–1742.
  25. Khanna G, Bushnell D, O’Dorisio MS: Utility of radiolabeled somatostatin receptor analogues for staging/restaging and treatment of somatostatin receptor-positive pediatric tumors. Oncologist 2008;13:382–389.
  26. Leja J, Yu D, Nilsson B, Gedda L, Zieba A, Hakkarainen T, Akerstrom G, Oberg K, Giandomenico V, Essand M: Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells. Gene Ther 2011;18:1052–1062.
  27. Yu D, Jin C, Leja J, Majdalani N, Nilsson B, Eriksson F, Essand M: Adenovirus modified with a cell-penetrating peptide in the hexon exhibits therapeutic effect in experimental neuroblastoma and neuroendocrine tumors. J Virol 2011;85:13114–13123.
  28. Cheung IY, Lo Piccolo MS, Kushner BH, Kramer K, Cheung NK: Quantitation of GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction: clinical utility in evaluating adjuvant therapy in neuroblastoma. J Clin Oncol 2003;21:1087–1093.
  29. Navid F, Santana VM, Barfield RC: Anti-GD2 antibody therapy for GD2-expressing tumors. Curr Cancer Drug Targets 2010;10:200–209.
  30. Kozbor D: Cancer vaccine with mimotopes of tumor-associated carbohydrate antigens. Immunol Res 2010;46:23–31.
  31. Hedborg F, Fischer-Colbrie R, Ostlin N, Sandstedt B, Tran MG, Maxwell PH: Differentiation in neuroblastoma: diffusion-limited hypoxia induces neuroendocrine secretory protein 55 and other markers of a chromaffin phenotype. PLoS One 2010;5:pii, e12825.
  32. Georgantzi K, Tsolakis AV, Stridsberg M, Jakobson A, Christofferson R, Janson ET: Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma. Pediatr Blood Cancer 2011;56:584–589.
  33. Lyons M, Onion D, Green NK, Aslan K, Rajaratnam R, Bazan-Peregrino M, Phipps S, Hale S, Mautner V, Seymour LW, Fisher KD: Adenovirus type 5 interactions with human blood cells may compromise systemic delivery. Mol Ther 2006;14:118–128.
  34. Fisher K: Striking out at disseminated metastases: the systemic delivery of oncolytic viruses. Curr Opin Mol Ther 2006;8:301–313.
  35. Danielsson A, Elgue G, Nilsson BM, Nilsson B, Lambris JD, Totterman TH, Kochanek S, Kreppel F, Essand M: An ex vivo loop system models the toxicity and efficacy of PEGylated and unmodified adenovirus serotype 5 in whole human blood. Gene Ther 2010;17:752–762.
  36. Kreppel F, Kochanek S: Modification of adenovirus gene transfer vectors with synthetic polymers: a scientific review and technical guide. Mol Ther 2008;16:16–29.
  37. Muthana M, Giannoudis A, Scott SD, Fang HY, Coffelt SB, Morrow FJ, Murdoch C, Burton J, Cross N, Burke B, Mistry R, Hamdy F, Brown NJ, Georgopoulos L, Hoskin P, Essand M, Lewis CE, Maitland NJ: Use of macrophages to target therapeutic adenovirus to human prostate tumors. Cancer Res 2011;71:1805–1815.
  38. Burke B, Sumner S, Maitland N, Lewis CE: Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. J Leukoc Biol 2002;72:417–428.
  39. Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, Battula VL, Weil M, Andreeff M, Marini FC: Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009;27:2614–2623.
  40. Garcia-Castro J, Alemany R, Cascallo M, Martinez-Quintanilla J, Arriero Mdel M, Lassaletta A, Madero L, Ramirez M: Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther 2010;17:476–483.
  41. Pesonen S, Helin H, Nokisalmi P, Escutenaire S, Ribacka C, Sarkioja M, Cerullo V, Guse K, Bauerschmitz G, Laasonen L, Kantola T, Ristimaki A, Rajecki M, Oksanen M, Haavisto E, Kanerva A, Joensuu T, Hemminki A: Oncolytic adenovirus treatment of a patient with refractory neuroblastoma. Acta Oncol 2010;49:117–119.
  42. Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, Daniels G, Gonzalez R, Glaspy J, Whitman E, Harrington K, Goldsweig H, Marshall T, Love C, Coffin R, Nemunaitis JJ: Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol 2009;27:5763–5771.
  43. Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, Oh SY, Han SY, Yoon JH, Hong SH, Moon A, Speth K, Park C, Ahn YJ, Daneshmand M, Rhee BG, Pinedo HM, Bell JC, Kirn DH: Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol 2008;9:533–542.
  44. Bridle BW, Stephenson KB, Boudreau JE, Koshy S, Kazdhan N, Pullenayegum E, Brunelliere J, Bramson JL, Lichty BD, Wan Y: Potentiating cancer immunotherapy using an oncolytic virus. Mol Ther 2010;18:1430–1439.
  45. Parikh NS, Currier MA, Mahller YY, Adams LC, Di Pasquale B, Collins MH, Cripe TP: Oncolytic herpes simplex virus mutants are more efficacious than wild-type adenovirus type 5 for the treatment of high-risk neuroblastomas in preclinical models. Pediatr Blood Cancer 2005;44:469–478.
  46. Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, Crombleholme TM, Cripe TP: Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res 2008;68:1170–1179.
  47. Mahller YY, Williams JP, Baird WH, Mitton B, Grossheim J, Saeki Y, Cancelas JA, Ratner N, Cripe TP: Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus. PLoS One 2009;4:e4235.
  48. Guffey MB, Parker JN, Luckett WS Jr, Gillespie GY, Meleth S, Whitley RJ, Markert JM: Engineered herpes simplex virus expressing bacterial cytosine deaminase for experimental therapy of brain tumors. Cancer Gene Ther 2007;14:45–56.
  49. Li H, Dutuor A, Tao L, Fu X, Zhang X: Virotherapy with a type 2 herpes simplex virus-derived oncolytic virus induces potent antitumor immunity against neuroblastoma. Clin Cancer Res 2007;13:316–322.
  50. Reddy PS, Burroughs KD, Hales LM, Ganesh S, Jones BH, Idamakanti N, Hay C, Li SS, Skele KL, Vasko AJ, Yang J, Watkins DN, Rudin CM, Hallenbeck PL: Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers. J Natl Cancer Inst 2007;99:1623–1633.
  51. Wadhwa L, Hurwitz MY, Chevez-Barrios P, Hurwitz RL: Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus. Cancer Res 2007;67:10653–10656.
  52. Morton CL, Houghton PJ, Kolb EA, Gorlick R, Reynolds CP, Kang MH, Maris JM, Keir ST, Wu J, Smith MA: Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. Pediatr Blood Cancer 2010;55:295–303.
  53. Yu L, Baxter PA, Zhao X, Liu Z, Wadhwa L, Zhang Y, Su JM, Tan X, Yang J, Adesina A, Perlakyl L, Hurwitz M, Idamakanti N, Police SR, Hallenbeck PL, Blaney SM, Chintagumpala M, Hurwitz RL, Li XN: A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models. Neuro Oncol 2011;13:14–27.
  54. Rudin CM, Poirier JT, Senzer NN, Stephenson J Jr, Loesch D, Burroughs KD, Reddy PS, Hann CL, Hallenbeck PL: Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features. Clin Cancer Res 2011;17:888–895.