Clinical testing of engineered oncolytic measles virus strains in the treatment of cancer: An overview

Current Opinion in Molecular Therapeutics

Volumn 11, Issue 1, 2009, Pages 43-53

  Msaouel, P ^a,b   Dispenzieri, A ^a   Galanis, E ^a  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF ATHENS   (Greece)

Author keywords

Brain tumor; Clinical trial; Measles virus; Multiple myeloma; Ovarian cancer; Virotherapy

Indexed keywords

ALPHA INTERFERON; CARCINOEMBRYONIC ANTIGEN; CYCLOPHOSPHAMIDE; IODINE 131; MEASLES VACCINE; MEMBRANE COFACTOR PROTEIN; ONCOLYTIC VIRUS; SODIUM IODIDE SYMPORTER;

ABDOMINAL PAIN; ANOREXIA; CANCER THERAPY; CLINICAL TRIAL; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FEVER; GENE EXPRESSION; GENE OVEREXPRESSION; GENE REPLICATION; GLIOBLASTOMA; HUMAN; IMAGING; MEASLES VIRUS; MEDICAL INFORMATION; MONITORING; MULTIPLE MYELOMA; NAUSEA; NONHUMAN; ONCOLYTIC VIROTHERAPY; OVARY CANCER; PAIN; REVIEW; TUMOR CELL; VIRUS GENE; VIRUS STRAIN;

ANIMALS; BRAIN NEOPLASMS; FEMALE; HUMANS; MEASLES VIRUS; MULTIPLE MYELOMA; NEOPLASMS; ONCOLYTIC VIROTHERAPY; ONCOLYTIC VIRUSES; OVARIAN NEOPLASMS;

MEASLES VIRUS;

EID: 58849107795     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (71)

1. Edelstein ML, Abedi MR, Wixon J: Gene therapy clinical trials worldwide to 2007 - An update. J Gene Med (2007) 9(10):833- 842.
2. Liu TC, Galanis E, Kirn D: Clinical trial results with oncolytic virotherapy: A century of promise, a decade of progress. Nat Clin Pract Oncol (2007) 4(2):101-117.
3. Kelly E, Russell SJ: History of oncolytic viruses: Genesis to genetic engineering. Mol Ther (2007) 15(4):651-659.
4. Bluming AZ, Ziegler JL: Regression of Burkitt's lymphoma in association with measles infection. Lancet (1971) 2(7715):105-106.
5. Gross S: Measles and leukaemia. Lancet (1971) 1(7695):397-398.
6. Mota HC: Infantile Hodgkin's disease: Remission after measles. Br Med J (1973) 2(5863):421.
7. Pasquinucci G: Possible effect of measles on leukaemia. Lancet (1971) 1(7690):136.
8. Zygiert Z: Hodgkin's disease: Remissions after measles. Lancet (1971) 1(7699):593.
9. Hernandez SA: Observacion de un caso de enfermedad de Hodgkin, con regresion de los sintomas e infartos ganglionares, post-sarampion. Arch Cubanos Cancer (1949) 8:26-31.
10. Southam CM: Present status of oncolytic virus studies. Trans NY Acad Sci (1960) 22:657-673.
11. Nakamura T, Peng KW, Harvey M, Greiner S, Lorimer IA, James CD, Russell SJ: Rescue and propagation of fully retargeted oncolytic measles viruses. Nat Biotechnol (2005) 23(2):209-214. •• This paper describes the development of the pseudoreceptor STAR system that allows rescue and propagation of fully retargeted MV-Edm strains.
12. Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dötsch C, Christiansen G, Billeter MA: Rescue of measles viruses from cloned DNA. EMBO J (1995) 14(23):5773-5784. •• This paper first established a system for rescuing measles viruses from cloned DNA without relying on any helper virus.
13. Yanagi Y, Takeda M, Ohno S: Measles virus: Cellular receptors, tropism and pathogenesis. J Gen Virol (2006) 87(10):2767-2779.
14. Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D: Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol (1993) 67(10):6025-6032.
15. Dorig RE, Marcil A, Chopra A, Richardson CD: The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell (1993) 75(2):295-305.
16. Tatsuo H, Ono N, Tanaka K, Yanagi Y: SLAM (CDw150) is a cellular receptor for measles virus. Nature (2000) 406(6798):893-897.
17. Jurianz K, Ziegler S, Garcia-Schuler H, Kraus S, Bohana-Kashtan O, Fishelson Z, Kirschfink M: Complement resistance of tumor cells: Basal and induced mechanisms. Mol Immunol (1999) 36(13-14):929-939.
18. Fishelson Z, Donin N, Zell S, Schultz S, Kirschfink M: Obstacles to cancer immunotherapy: Expression of membrane complement regulatory proteins (mCRPs) in tumors. Mol Immunol (2003) 40(2-4):109-123.
19. Wild TF, Malvoisin E, Buckland R: Measles virus: Both the haemagglutinin and fusion glycoproteins are required for fusion. J Gen Virol (1991) 72(2):439-442.
20. No authors listed: Live attenuated measles vaccine. EPI Newsl (1980) 2(1):6.
21. Hilleman MR: Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications. Vaccine (2001) 20(5-6):651-665.
22. Cutts FT, Markowitz LE: Successes and failures in measles control. J Infect Dis (1994) 170(Suppl 1):S32-S41.
23. Anderson BD, Nakamura T, Russell SJ, Peng KW: High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus. Cancer Res (2004) 64(14):4919-4926. • This study suggested that variations in CD46 density determine the tumor-specificity of MV-Edm strains.
24. Peng KW, Donovan KA, Schneider U, Cattaneo R, Lust JA, Russell SJ: Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker. Blood (2003) 101(7):2557-2562.
25. Phuong LK, Allen C, Peng KW, Giannini C, Greiner S, TenEyck CJ, Mishra PK, Macura SI, Russell SJ, Galanis EC: Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res (2003) 63(10):2462-2469. •• This paper describes the preclinical evaluation of MV-CEA efficacy against human glioblastoma multiforme xenografts. MV-CEA demonstrated potent therapeutic efficacy against gliomas in both subcutaneous and intracranial orthotopic mouse models.
26. Blechacz B, Splinter PL, Greiner S, Myers R, Peng KW, Federspiel MJ, Russell SJ, LaRusso NF: Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma. Hepatology (2006) 44(6):1465-1477. • This study investigated the antitumor effect of MV-CEA and MV-NIS against human hepatocellular carcinoma xenografts. Both viruses demonstrated significant therapeutic effect against hepatocellular carcinoma in vitro and in vivo.
27. 131[I] resulted in significant regression of MV-resistant tumors.
28. Peng KW, Ahmann GJ, Pham L, Greipp PR, Cattaneo R, Russell SJ: Systemic therapy of myeloma xenografts by an attenuated measles virus. Blood (2001) 98(7):2002-2007. •• This study investigated the antitumor effect of MV-Edm against human myeloma xenografts. The virus induced significant tumor regression.
29. Peng KW, Facteau S, Wegman T, O'Kane D, Russell SJ: Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med (2002) 8(5):527-531. •• This paper describes the generation and characterization of MV-CEA. Monitoring of viral gene expression kinetics was achievable by measuring CEA levels in blood serum.
30. Galanis E, Bateman A, Johnson K, Diaz RM, James CD, Vile R, Russell SJ: Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas. Hum Gene Ther (2001) 12(7):811-821.
31. Grote D, Russell SJ, Cornu TI, Cattaneo R, Vile R, Poland GA, Fielding AK: Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice. Blood (2001) 97(12):3746- 3754. • This study evaluated the antitumor effect of MV-Edm against human lymphoma xenografts. MV-Edm infection resulted in significant regression of large established human lymphoma xenografts.
32. Peng KW, TenEyck CJ, Galanis E, Kalli KR, Hartmann LC, Russell SJ: Intraperitoneal therapy of ovarian cancer using an engineered measles virus. Cancer Res (2002) 62(16):4656-4662. •• This paper describes the preclinical evaluation of MV-CEA efficacy against human ovarian cancer xenografts. MV-CEA demonstrated significant in vivo therapeutic benefits and viral gene expression could be monitored by serum CEA measurement.
33. Dingli D, Bergert ER, Bajzer Z, O'Connor MK, Russell SJ, Morris JC: Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter. Biochem Biophys Res Commun (2004) 325(1):157-166.
34. Dingli D, Russell SJ, Morris JC 3rd: In vivo imaging and tumor therapy with the sodium iodide symporter. J Cell Biochem (2003) 90(6):1079-1086.
35. Hasegawa K, Pham L, O'Connor MK, Federspiel MJ, Russell SJ, Peng KW: Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter. Clin Cancer Res (2006) 12(6):1868-1875.
36. McDonald CJ, Erlichman C, Ingle JN, Rosales GA, Allen C, Greiner SM, Harvey ME, Zollman PJ, Russell SJ, Galanis E: A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. Breast Cancer Res Treat (2006) 99(2):177-184. • This study determined the antitumor effect of MV-CEA against human breast cancer xenografts. Potent antitumor activity of MV-CEA against breast cancer cell lines and xenografts was demonstrated.
37. Msaouel P, Iankov ID, Allen C, Morris JC, von Messling V, Cattaneo R, Koutsilieris M, Russell SJ, Galanis E: Engineered measles virus as a novel oncolytic therapy against prostate cancer. Prostate (2009) 69(1):82-91. • This study determined the antitumor effect of MV-CEA against human prostate cancer xenografts. The virus demonstrated considerable oncolytic potency both in vitro and in vivo.
38. Peng KW, Hadac EM, Anderson BD, Myers R, Harvey M, Greiner SM, Soeffker D, Federspiel MJ, Russell SJ: Pharmacokinetics of oncolytic measles virotherapy: Eventual equilibrium between virus and tumor in an ovarian cancer xenograft model. Cancer Gene Ther (2006) 13(8):732-738.
39. Peng KW, Frenzke M, Myers R, Soeffker D, Harvey M, Greiner S, Galanis E, Cattaneo R, Federspiel MJ, Russell SJ: Biodistribution of oncolytic measles virus after intraperitoneal administration into Ifnar-CD46Ge transgenic mice. Hum Gene Ther (2003) 14(16):1565-1577.
40. Allen C, Paraskevakou G, Liu C, Iankov ID, Msaouel P, Zollman P, Myers R, Peng KW, Russell SJ, Galanis E: Oncolytic measles virus strains in the treatment of gliomas. Expert Opin Biol Ther (2008) 8(2):213-220.
41. Myers R, Harvey M, Kaufmann TJ, Greiner SM, Krempski JW, Raffel C, Shelton SE, Soeffker D, Zollman P, Federspiel MJ, Blanco M, Galanis E: Toxicology study of repeat intracerebral administration of a measles virus derivative producing carcinoembryonic antigen in rhesus macaques in support of a phase I/II clinical trial for patients with recurrent gliomas. Hum Gene Ther (2008) 19(7):690-698.
42. Myers RM, Greiner SM, Harvey ME, Griesmann G, Kuffel MJ, Buhrow SA, Reid JM, Federspiel M, Ames MM, Dingli D, SchweikartK et al: Preclinical pharmacology and toxicology of intravenous MV-NIS, an oncolytic measles virus administered with or without cyclophosphamide. Clin Pharmacol Ther (2007) 82(6):700-710. •• This paper describes a preclinical toxicology study of MV-NIS in support of a phase I clinical trial of multiple myeloma. Cyclophosphamide suppression of anti-measles immunity resulted in prolongation of MV-NIS persistence before clearance by the immune system.
43. Myers RM, Harvey ME, Greiner SM, Soeffker DC, Krempski JW, Zollman PJ, Shelton SE, Raffel C, Goerss SJ, Kaufmann JT, Federspiel MJ et al: Safety of repeat intracerebral administration of MV-CEA in Rhesus macaques in support of a phase I/II clinical trial for patients with recurrent gliomas. Mol Ther (2006) 13(S1): Abs 297.
44. Mrkic B, Odermatt B, Klein MA, Billeter MA, Pavlovic J, Cattaneo R: Lymphatic dissemination and comparative pathology of recombinant measles viruses in genetically modified mice. J Virol (2000) 74(3):1364-1372.
45. KO CD46 Ge mouse.
46. Roscic-Mrkic B, Schwendener RA, Odermatt B, Zuniga A, Pavlovic J, Billeter MA, Cattaneo R: Roles of macrophages in measles virus infection of genetically modified mice. J Virol (2001) 75(7):3343-3351.
47. Kemper C, Leung M, Stephensen CB, Pinkert CA, Liszewski MK, Cattaneo R, Atkinson JP: Membrane cofactor protein (MCP; CD46) expression in transgenic mice. Clin Exp Immunol (2001) 124(2):180-189.
48. Driesse MJ, Vincent AJ, Sillevis Smitt PA, Kros JM, Hoogerbrugge PM, Avezaat CJ, Valerio D, Bout A: Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: Toxicity study in nonhuman primates. Gene Ther (1998) 5(8):1122-1129.
49. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, Kaur B, Louis DN, Weissleder R, Caligiuri MA, Chiocca EA: Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci USA (2006) 103(34):12873-12878.
50. Kambara H, Saeki Y, Chiocca EA: Cyclophosphamide allows for in vivo dose reduction of a potent oncolytic virus. Cancer Res (2005) 65(24):11255-11258.
51. Lamfers ML, Fulci G, Gianni D, Tang Y, Kurozumi K, Kaur B, Moeniralm S, Saeki Y, Carette JE, Weissleder R, Vandertop WP et al: Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging. Mol Ther (2006) 14(6):779-788.
52. Hsu EC, Dörig RE, Sarangi F, Marcil A, Iorio C, Richardson CD: Artificial mutations and natural variations in the CD46 molecules from human and monkey cells define regions important for measles virus binding. J Virol (1997) 71(8):6144-6154.
53. NCT00408590: Oncolytic virus therapy in treating patients with progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer. NIH, Bethesda, MD, USA (2008): October 27. http://www.clinicaltrials.gov/ct2/show/NCT00408590 •• The design of the phase I clinical trial of MV-CEA in patients with recurrent ovarian cancer is described.
54. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst (2000) 92(3):205-216.
55. 50.
56. NCT00390299: Viral therapy in treating patients with recurrent glioblastoma multiforme. NIH, Bethesda, MD, USA (2008). http://www. clinicaltrials.gov/ct2/show/NCT00390299 •• The study rationale, design, and accrual criteria of the phase I clinical trial of MV-CEA in patients with recurrent glioblastoma multiforme are described.
57. NCT00450814: Vaccine therapy with or without cyclophosphamide in treating patients with recurrent or refractory multiple myeloma. NIH, Bethesda, MD, USA (2008). http://www.clinicaltrials.gov/ct2/show/ NCT00450814 •• The study rationale, design, and accrual criteria of the phase I clinical trial of MV-NIS in patients with recurrent or refractory multiple myeloma are described.
58. Heinzerling L, Künzi V, Oberholzer PA, Kündig T, Naim H, Dummer R: Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. Blood (2005) 106(7):2287-2294. •• This paper reports results of a phase I, open-label, non-randomized, dose-escalation clinical trial of the unmodified MV vaccine strain MV-EZ in patients with CTCLs. Early signs of biological activity were observed, including complete tumor regression of one CTCL lesion. The treatment was well tolerated at all dose levels, with minimal toxicity after intratumoral administration.
59. Ikeda K, Ichikawa T, Wakimoto H, Silver JS, Deisboeck TS, Finkelstein D, Harsh GR 4th, Louis DN, Bartus RT, Hochberg FH, Chiocca EA: Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med (1999) 5(8):881-887.
60. Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, Thompson J, Selby P, de Bono J, Melcher A, Pandha H et al: Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clin Cancer Res (2008) 14(1):259-269.
61. Iankov ID, Blechacz B, Liu C, Schmeckpeper JD, Tarara JE, Federspiel MJ, Caplice N, Russell SJ: Infected cell carriers: A new strategy for systemic delivery of oncolytic measles viruses in cancer virotherapy. Mol Ther (2007) 15(1):114-122.
62. Ong HT, Hasegawa K, Dietz AB, Russell SJ, Peng KW: Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies. Gene Ther (2007) 14(4):324-333.
63. Munguia A, Ota T, Miest T, Russell SJ: Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth. Gene Ther (2008) 15(10):797-806.
64. Liu C, Sarkaria JN, Petell CA, Paraskevakou G, Zollman PJ, Schroeder M, Carlson B, Decker PA, Wu W, James CD, Russell SJ et al: Combination of measles virus virotherapy and radiation therapy has synergistic activity in the treatment of glioblastoma multiforme. Clin Cancer Res (2007) 13(23):7155-7165.
65. Liu C, Erlichman C, McDonald CJ, Ingle JN, Zollman P, Iankov I, Russell SJ, Galanis E: Heat shock protein inhibitors increase the efficacy of measles virotherapy. Gene Ther (2008) 15(14):1024-1034.
66. Nussbaum O, Broder CC, Moss B, Stern LB, Rozenblatt S, Berger EA: Functional and structural interactions between measles virus hemagglutinin and CD46. J Virol (1995) 69(6):3341-3349.
67. Nakamura T, Peng KW, Vongpunsawad S, Harvey M, Mizuguchi H, Hayakawa T, Cattaneo R, Russell SJ: Antibody-targeted cell fusion. Nat Biotechnol (2004) 22(3):331-336. • This study demonstrated that cells can fuse after MV-Edm retargeting and ablation of entry through CD46 and SLAM.
68. Vongpunsawad S, Oezgun N, Braun W, Cattaneo R: Selectively receptor-blind measles viruses: Identification of residues necessary for SLAM- or CD46-induced fusion and their localization on a new hemagglutinin structural model. J Virol (2004) 78(1):302-313.
69. Allen C, Vongpunsawad S, Nakamura T, James CD, Schroeder M, Cattaneo R, Giannini C, Krempski J, Peng KW, Goble JM, Uhm JH et al: Retargeted oncolytic measles strains entering via the EGFRvIII receptor maintain significant antitumor activity against gliomas with increased tumor specificity. Cancer Res (2006) 66(24):11840-11850. • This paper describes the engineering of a retargeted MV-Edm strain designed to display a single-chain antibody against EGFRvIII. The EGFRvIII-retargeted virus demonstrated comparable therapeutic efficacy to the unmodified MV-GFP strain against EGFRvIII-expressing glioma lines.
70. G, Allen C, Nakamura T, Zollman P, James CD, Peng KW, Schroeder M, Russell SJ, Galanis E: Epidermal growth factor receptor (EGFR)-retargeted measles virus strains effectively target EGFR- or EGFRvIII expressing gliomas. Mol Ther (2007) 15(4):677-686. • This paper describes the design of a retargeted MV-Edm strain engineered to display a single-chain antibody against EGFR. The EGFR-retargeted virus demonstrated comparable therapeutic efficacy to the unmodified virus in glioma cells overexpressing EGFR or EGFRvIII.
71. Allen C, Paraskevakou G, Iankov I, Schroeder M, Puri RK, Russell SJ, Galanis E: IL13 displaying retargeted oncolytic measles virus (MV) strains have significant activity and improved therapeutic index against gliomas. Mol Ther (2007) 15(Suppl 1s): Abs 51. • This paper describes the engineering of a retargeted MV-Edm strain designed to display a natural ligand (IL-13). The retargeted virus demonstrated comparable therapeutic efficacy and improved specificity compared with the unmodified MV strain MV-GFP.