Horm Metab Res 2011; 43(12): 877-883
DOI: 10.1055/s-0031-1277225
Review

© Georg Thieme Verlag KG Stuttgart · New York

Oncolytic Viruses for the Treatment of Neuroendocrine Tumors

M. Essand1 , J. Leja1 , V. Giandomenico2 , K. E. Öberg2
  • 1Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  • 2Department of Medical Sciences, Division of Endocrine Oncology, Science for Life Laboratory, Uppsala University and Center of Excellence for Endocrine Tumors, University Hospital, Uppsala, Sweden
Further Information

Publication History

received 07.02.2011

accepted 20.04.2011

Publication Date:
30 May 2011 (online)

Abstract

Oncolytic viruses are emerging as anticancer agents, and they have also shown great promise for use against neuroendocrine tumors. Many viruses have a natural tropism for replication in tumor cells. Others can be genetically engineered to selectively kill tumor cells. Viruses have some advantages as therapeutic agents over current cytotoxic drugs and small molecules. They replicate in tumor cells and thereby increase in number over time leading to increased dosage. They are immunogenic and can alter the immunosuppressive tumor microenvironment and activate immune effector cells. They have also been shown to be able to kill drug-resistant cancer stem cells. This article reviews the recent literature on oncolytic viruses used so far for neuroendocrine tumors and indicates important issues to focus on in the future.

References

  • 1 Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours.  Lancet Oncol. 2008;  9 61-72
  • 2 Oberg K. Gastric neuroendocrine cells and secretory products.  Yale J Biol Med. 1998;  71 149-154
  • 3 Modlin IM, Kidd M, Pfragner R, Eick GN, Champaneria MC. The functional characterization of normal and neoplastic human enterochromaffin cells.  J Clin Endocrinol Metab. 2006;  91 2340-2348
  • 4 Gustafsson BI, Kidd M, Modlin IM. Neuroendocrine tumors of the diffuse neuroendocrine system.  Curr Opin Oncol. 2008;  20 1-12
  • 5 Andrew A, Kramer B, Rawdon BB. The origin of gut and pancreatic neuroendocrine (APUD) cells – the last word?.  J Pathol. 1998;  186 117-118
  • 6 Rindi G, Capella C, Solcia E. Cell biology, clinicopathological profile, and classification of gastro-enteropancreatic endocrine tumors.  J Mol Med. 1998;  76 413-420
  • 7 O’Grady HL, Conlon KC. Pancreatic neuroendocrine tumours.  Eur J Surg Oncol. 2008;  34 324-332
  • 8 Welin S, Stridsberg M, Cunningham J, Granberg D, Skogseid B, Oberg K, Eriksson B, Janson ET. Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors.  Neuroendocrinology. 2009;  89 302-307
  • 9 van der Horst-Schrivers AN, Wymenga AN, Links TP, Willemse PH, Kema IP, de Vries EG. Complications of midgut carcinoid tumors and carcinoid syndrome.  Neuroendocrinology. 2004;  80 (Suppl) 28-32
  • 10 Rekhtman N. Neuroendocrine tumors of the lung: an update.  Arch Pathol Lab Med. 2010;  134 1628-1638
  • 11 Cerilli LA, Ritter JH, Mills SE, Wick MR. Neuroendocrine neoplasms of the lung.  Am J Clin Pathol. 2001;  116 (Suppl) S65-S96
  • 12 Moran CA, Suster S, Coppola D, Wick MR. Neuroendocrine carcinomas of the lung: a critical analysis.  Am J Clin Pathol. 2009;  131 206-221
  • 13 Tsuta K, Raso MG, Kalhor N, Liu DD, Wistuba II, Moran CA. Histologic features of low- and intermediate-grade neuroendocrine carcinoma (typical and atypical carcinoid tumors) of the lung.  Lung Cancer. 2011;  71 34-41
  • 14 Pitt SC, Moley JF. Medullary, anaplastic, and metastatic cancers of the thyroid.  Semin Oncol. 2010;  37 567-579
  • 15 Marsh DJ, Learoyd DL, Robinson BG. Medullary thyroid carcinoma: recent advances and management update.  Thyroid. 1995;  5 407-424
  • 16 Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma.  Lancet. 2007;  369 2106-2120
  • 17 Maris JM. Recent advances in neuroblastoma.  N Engl J Med. 2010;  362 2202-2211
  • 18 George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC, Pulsipher M, Grupp SA, Diller L. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update.  J Clin Oncol. 2006;  24 2891-2896
  • 19 Eriksson B, Kloppel G, Krenning E, Ahlman H, Plockinger U, Wiedenmann B, Arnold R, Auernhammer C, Korner M, Rindi G, Wildi S. Consensus guidelines for the management of patients with digestive neuroendocrine tumors – well-differentiated jejunal-ileal tumor/carcinoma.  Neuroendocrinology. 2008;  87 8-19
  • 20 Nilsson O, Arvidsson Y, Johanson V, Forssell-Aronsson E, Ahlman H. New medical strategies for midgut carcinoids.  Anticancer Agents Med Chem. 2010;  10 250-269
  • 21 Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, Marx SJ, Pasieka JL, Pommier RF, Yao JC, Jensen RT. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas.  Pancreas. 2010;  39 735-752
  • 22 Bertino EM, Confer PD, Colonna JE, Ross P, Otterson GA. Pulmonary neuroendocrine/carcinoid tumors: a review article.  Cancer. 2009;  115 4434-4441
  • 23 Hong DS, Cabanillas ME, Wheler J, Naing A, Tsimberidou AM, Ye L, Waguespack SG, Hernandez M, El Naggar AK, Bidyasar S, Wright J, Sherman SI, Kurzrock R. Inhibition of the Ras/Raf/MEK/ERK and RET Kinase Pathways with the Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Medullary and Differentiated Thyroid Malignancies.  J Clin Endocrinol Metab. 2011;  96 997-1005
  • 24 McCormick F. Future prospects for oncolytic therapy.  Oncogene. 2005;  24 7817-7819
  • 25 Cattaneo R, Miest T, Shashkova EV, Barry MA. Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded.  Nat Rev Microbiol. 2008;  6 529-540
  • 26 Vattemi E, Claudio PP. Adenoviral gene therapy in head and neck cancer.  Drug News Perspect. 2006;  19 329-337
  • 27 Young LS, Searle PF, Onion D, Mautner V. Viral gene therapy strategies: from basic science to clinical application.  J Pathol. 2006;  208 299-318
  • 28 Ribacka C, Hemminki A. Virotherapy as an approach against cancer stem cells.  Curr Gene Ther. 2008;  8 88-96
  • 29 Endo Y, Sakai R, Ouchi M, Onimatsu H, Hioki M, Kagawa S, Uno F, Watanabe Y, Urata Y, Tanaka N, Fujiwara T. Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation.  Oncogene. 2008;  27 2375-2381
  • 30 Thirukkumaran CM, Nodwell MJ, Hirasawa K, Shi ZQ, Diaz R, Luider J, Johnston RN, Forsyth PA, Magliocco AM, Lee P, Nishikawa S, Donnelly B, Coffey M, Trpkov K, Fonseca K, Spurrell J, Morris DG. Oncolytic viral therapy for prostate cancer: efficacy of reovirus as a biological therapeutic.  Cancer Res. 70 2435-2444
  • 31 Garber K. China approves world's first oncolytic virus therapy for cancer treatment.  J Natl Cancer Inst. 2006;  98 298-300
  • 32 Berk AJ. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus.  Oncogene. 2005;  24 7673-7685
  • 33 Essand M. Gene therapy and immunotherapy of prostate cancer: adenoviral-based strategies.  Acta Oncol. 2005;  44 610-627
  • 34 Uchino J, Takayama K, Harada A, Kawakami Y, Inoue H, Curiel DT, Nakanishi Y. Infectivity enhanced, hTERT promoter-based conditionally replicative adenoviruses are useful for SCLC treatment.  Cancer Gene Ther. 2005;  12 737-748
  • 35 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
  • 36 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
  • 37 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;  April 14 [Epub ahead of print]
  • 38 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
  • 39 Wang H, Li ZY, Liu Y, Persson J, Beyer I, Moller T, Koyuncu D, Drescher MR, Strauss R, Zhang XB, Wahl  JK, 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
  • 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 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
  • 42 Keshelava N, Seeger RC, Groshen S, Reynolds CP. Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy.  Cancer Res. 1998;  58 5396-5405
  • 43 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
  • 44 Ara T, Fukuzawa M, Kusafuka T, Komoto Y, Oue T, Inoue M, Okada A. Immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in neuroblastoma: association with tumor progression and clinical outcome.  J Pediatr Surg. 1998;  33 1272-1278
  • 45 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
  • 46 Shah AC, Parker JN, Gillespie GY, Lakeman FD, Meleth S, Markert JM, Cassady KA. Enhanced antiglioma activity of chimeric HCMV/HSV-1 oncolytic viruses.  Gene Ther. 2007;  14 1045-1054
  • 47 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
  • 48 Fukuhara H, Ino Y, Kuroda T, Martuza RL, Todo T. Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system.  Cancer Res. 2005;  65 10663-10668
  • 49 Ino Y, Saeki Y, Fukuhara H, Todo T. Triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor efficacy.  Clin Cancer Res. 2006;  12 643-652
  • 50 Guffey MB, Parker JN, Luckett Jr WS, 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
  • 51 Messerli SM, Prabhakar S, Tang Y, Mahmood U, Giovannini M, Weissleder R, Bronson R, Martuza R, Rabkin S, Breakefield XO. Treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2.  Hum Gene Ther. 2006;  17 20-30
  • 52 Prabhakar S, Messerli SM, Stemmer-Rachamimov AO, Liu TC, Rabkin S, Martuza R, Breakefield XO. Treatment of implantable NF2 schwannoma tumor models with oncolytic herpes simplex virus G47Delta.  Cancer Gene Ther. 2007;  14 460-467
  • 53 Prabhakar S, Brenner GJ, Sung B, Messerli SM, Mao J, Sena-Esteves M, Stemmer-Rachamimov A, Tannous B, Breakefield XO. Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter.  Cancer Gene Ther. 2010;  17 266-274
  • 54 Burkhart CG. Herpes and acoustic neuromas: is there a cause and effect to observe?.  Med Hypotheses. 2010;  74 1013-1014
  • 55 Yu Z, Eisenberg DP, Singh B, Shah JP, Fong Y, Wong RJ. Treatment of aggressive thyroid cancer with an oncolytic herpes virus.  Int J Cancer. 2004;  112 525-532
  • 56 Sivendran S, Pan M, Kaufman HL, Saenger Y. Herpes simplex virus oncolytic vaccine therapy in melanoma.  Expert Opin Biol Ther. 2010;  10 1145-1153
  • 57 Zemp FJ, Corredor JC, Lun X, Muruve DA, Forsyth PA. Oncolytic viruses as experimental treatments for malignant gliomas: using a scourge to treat a devil.  Cytokine Growth Factor Rev. 2010;  21 103-117
  • 58 Hales LM, Knowles NJ, Reddy PS, Xu L, Hay C, Hallenbeck PL. Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus.  J Gen Virol. 2008;  89 1265-1275
  • 59 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
  • 60 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
  • 61 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
  • 62 Yu L, Baxter PA, Zhao X, Liu Z, Wadhwa L, Zhang Y, Su JM, Tan X, Yang J, Adesina A, Perlaky 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
  • 63 Venkataraman S, Reddy SP, Loo J, Idamakanti N, Hallenbeck PL, Reddy VS. Structure of Seneca Valley Virus-001: an oncolytic picornavirus representing a new genus.  Structure. 2008;  16 1555-1561
  • 64 Venkataraman S, Reddy SP, Loo J, Idamakanti N, Hallenbeck PL, Reddy VS. Crystallization and preliminary X-ray diffraction studies of Seneca Valley virus-001, a new member of the Picornaviridae family.  Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008;  64 293-296
  • 65 Haley SA, O’Hara BA, Banerjee R, Atwood WJ. Unique susceptibility of a human lung carcinoid tumor cell line to infection with BK virus.  Virus Res. 2010;  149 128-132
  • 66 Szeberenyi J, Fabian Z, Torocsik B, Kiss K, Csatary LK. Newcastle disease virus-induced apoptosis in PC12 pheochromocytoma cells.  Am J Ther. 2003;  10 282-288
  • 67 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

Correspondence

Prof. M. Essand

Department of Immunology

Genetics and Pathology

75185 Uppsala

Sweden

Phone: +46/18/611 0223

Fax: +46/18/611 0222

Email: magnus.essand@igp.uu.se

Prof. Kjell E. Öberg

Division of Endocrine Oncology

University Hospital

75185 Uppsala

Sweden

Phone: +46/18/611 4917

Fax: +46/18/507 268

Email: kjell.oberg@medsci.uu.se

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