Advanced SearchSearch Tips
Naturally occurring reoviruses for human cancer therapy
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 48, Issue 8,  2015, pp.454-460
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.8.076
 Title & Authors
Naturally occurring reoviruses for human cancer therapy
Kim, Manbok;
  PDF(new window)
Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]
Attenuated reovirus;Oncogene;Oncolytic virus;Reovirus;Tumor suppressor gene;
 Cited by
Reovirus safety study for proliferation and differentiation of human adipose-derived mesenchymal stem cells, Journal of Microbiology, 2017, 55, 1, 75  crossref(new windwow)
Kim M (2015) Replicating poxviruses for human cancer therapy. J Microbiol 53, 209-218 crossref(new window)

Roberts MS, Lorence RM, Groene WS and Bamat MK (2006) Naturally oncolytic viruses. Curr Opin Mol Ther 8, 314-321

Wang G, Barrett JW, Stanford M et al (2006) Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor. Proc Natl Acad Sci U S A 103, 4640-4645 crossref(new window)

Strong JE, Coffey MC, Tang D, Sabinin P and Lee PW (1998) The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J 17, 3351-3362 crossref(new window)

Kim M, Williamson CT, Prudhomme J et al (2010) The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene 29, 3990-3996 crossref(new window)

Tyler KL (2001) Mammalian reoviruses, p. 1729-1745. In B.N. Fields, D.M. Knipe, and P.M. Howley (eds), Fields Virology, Lippincott-Raven, Philadelphia, USA

Ramig RF, Cross RK, and Fields BN (1977) Genome RNAs and polypeptides of reovirus serotypes 1, 2, and 3. J Virol 22, 726-733

Stanley NF, Dorman DC and Ponsford J (1953) Studies on the pathogenesis of a hitherto undescribed virus (hepato-encephalomyelitis) producing unusual symptoms in suckling mice. Aust J Exp Biol Med Sci 31, 147-159 crossref(new window)

Sabin AB. Reoviruses (1959) A new group of respiratory and enteric viruses formerly classified as ECHO type 10 is described. Science 130, 1387-1389 crossref(new window)

Stanley NF (1961) Relationship of Hepatoencephalomyelitis Virus and Reoviruses. letters to Nature 189, 687 crossref(new window)

Ramos-Alvarez M and Sabin AB (1954) Characteristics of poliomyelitis and other enteric viruses recovered in tissue culture from healthy American children. Proc Soc Exp Biol Med 87, 655-661 crossref(new window)

Stoeckel J and Hay JG (2006) Drug evaluation: Reolysin--wild-type reovirus as a cancer therapeutics. Curr Opin Mol Ther 8, 249-260

Ramos-Alvarez M and Sabin AB (1958) Enteropathogenic viruses and bacteria. Role in summer diarrheal diseases of infancy and early childhood. Jour Amer Med Ass'n 167, 147-156 crossref(new window)

Jackson GG, Muldoon BL and Cooper GS (1961) Reovirus type 1 as an etiologic agent of the common cold. Jour Clin Invest 40, 1051

Ramos-Alvarez M and Sabin AB (1956) Intestinal viral flora of healthy children demonstrable by monkey kidney tissue culture. Amer Jour Pub Health 46, 295-299 crossref(new window)

Rosen L, Evans HE and Spickard A (1963) Reovirus infections in human volunteers Am J Hyg 77, 29-37

Vidal L, Pandha HS, Yap TA et al (2008) A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin Cancer Res 14, 7127-7137 crossref(new window)

Bennette JG (1960) Isolation of a Non-pathogenic Tumour-destroying Virus from Mouse Ascites. Nature 187, 72-73 crossref(new window)

Nelson JB and Tarnowski GS (1960) An Oncolytic Virus recovered from Swiss Mice during Passage of an Ascites Tumour. Nature 188, 866-867 crossref(new window)

Bennette JG, Bush PV and Steele RD (1967) Characteristics of a newborn runt disease induced by neonatal infection with an oncolytic strain of reovirus type 3 (REO3MH). I. Pathological investigations in rats and mice. Br J Exp Pathol 48, 251-266

Hashiro G, Loh PC and Yau JT (1977) The preferential cytotoxicity of reovirus for certain transformed cell lines. Arch Virol 54, 307-315 crossref(new window)

Duncan MR, Stanish SM and Cox DC (1978) Differential sensitivity of normal and transformed human cells to reovirus infection. J Virol 28, 444-449

Strong JE, Coffey MC, Tang D, Sabinin P and Lee PW (1998) The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J 17, 3351-3362 crossref(new window)

Coffey MC, Strong JE, Forsyth PA and Lee PW (1998) Reovirus therapy of tumors with activated Ras pathway. Science 282, 1332-1334 crossref(new window)

Kim M, Chung YH and Johnston RN (2007) Reovirus and tumor oncolysis. J Microbiol 45, 187-192

Kuttler F and Mai S (2006) c-Myc, Genomic Instability and Disease. Genome Dyn 1, 171-190

Prochownik EV and Li Y (2007) The ever expanding role for c-Myc in promoting genomic instability. Cell Cycle 6, 1024-1029 crossref(new window)

Prochownik EV (2008) c-Myc: linking transformation and genomic instability. Curr Mol Med 8, 446-458 crossref(new window)

Coschi CH and Dick FA (2012) Chromosome instability and deregulated proliferation: an unavoidable duo. Cell Mol Life Sci 69, 2009-2024 crossref(new window)

Holohan C, Van Schaeybroeck S, Longley DB and Johnston PG (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13, 714-726 crossref(new window)

Kim M, Egan C, Alain T et al (2007) Acquired resistance to reoviral oncolysis in Ras-transformed fibrosarcoma cells. Oncogene 26, 4124-4134 crossref(new window)

Alain T, Kim M, Johnston RN et al (2006) The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro. Br J Cancer 95, 1020-1027 crossref(new window)

Loken SD, Norman K, Hirasawa K, Nodwell M, Lester WM and Demetrick DJ (2004) Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (dearing 3) as an anticancer biotherapeutics. Cancer Biol Ther 3, 734-738 crossref(new window)

Kim M, Garant KA, zur Nieden NI et al (2011) Attenuated reovirus displays oncolysis with reduced host toxicity. Br J Cancer 104, 290-299 crossref(new window)

Kim M and Johnston RN (2014) Tumor suppressor-based susceptibility of hyperproliferative cells to oncolytic viral therapy. Chinese patent No.: 200980126543.5 Date of Patent grant: July 30, 2014

Lolkema MP, Arkenau HT, Harrington K et al (2011) A phase I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin Cancer Res 17, 581-588 crossref(new window)

Comins C, Spicer J, Protheroe A et al (2010) REO-10: a phase I study of intravenous reovirus and docetaxel in patients with advanced cancer. Clin Cancer Res 16, 5564-5572 crossref(new window)

Alloussi SH, Alkassar M, Urbschat S, Graf N and Gärtner B (2011) All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma. Oncol Rep 26, 645-649

Minuk GY, Paul RW and Lee PW (1985) The prevalence of antibodies to reovirus type 3 in adults with idiopathic cholestatic liver disease. J Med Virol 16, 55-60 crossref(new window)

Minuk GY, Rascanin N, Paul RW, Lee PW, Buchan K and Kelly JK (1987) Reovirus type 3 infection in patients with primary biliary cirrhosis and primary sclerosing cholangitis. J Hepatol 5, 8-13 crossref(new window)

Le Boeuf F, Diallo JS, McCart JA et al (2010) Synergistic interaction between oncolytic viruses augments tumor killing. Mol Ther 18, 888-895 crossref(new window)

Alkassar M, Gärtner B, Roemer K et al (2011) The combined effects of oncolytic reovirus plus Newcastle disease virus and reovirus plus parvovirus on U87 and U373 cells in vitro and in vivo. J Neurooncol 104, 715-727 crossref(new window)

Forsyth P, Roldán G, George D et al (2008) A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther 16, 627-632 crossref(new window)

Karapanagiotou EM, Roulstone V, Twigger K et al (2012) Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies. Clin Cancer Res 18, 2080-2089 crossref(new window)

Galanis E, Markovic SN, Suman VJ et al (2012) Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. Mol Ther 20, 1998-2003 crossref(new window)

Morris DG, Feng X, DiFrancesco LM et al (2013) REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors. Invest New Drugs 31, 696-706 crossref(new window)

Harrington KJ, Karapanagiotou EM, Roulstone V et al (2010) Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clin Cancer Res 16, 3067-3077 crossref(new window)

Kicielinski KP, Chiocca EA, Yu JS, Gill GM, Coffey M, Markert JM (2014) Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther 22, 1056-1062 crossref(new window)