Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC34410.15690/vramn.v67i2.121ONCOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ОНКОЛОГИИONCOLYTIC PARVOVIRUSES. A NEW APPROACHES FOR CANCER THERAPYОНКОЛИТИЧЕСКИЕ ПАРВОВИРУСЫ. НОВЫЕ ПОДХОДЫ К ЛЕЧЕНИЮ РАКОВЫХ ЗАБОЛЕВАНИЙLoktevV. B.ЛоктевВ. Б.
Russian Federation

доктор биологических наук, профессор, заведующий отделом молекулярной вирусо- логии флавивирусов и вирусных гепатитов ФБУН ГНЦ ВБ «Вектор» Адрес: 630559, Новосибирская область, пос. Кольцово Тел.: (383) 363-47-53, факс: (383) 363-74-09

loktev@vector.nsc.ruIvan'kinaT. Yu.ИванькинаТ. Ю.
Russian Federation

главный специалист отдела координации НИР и ОКР ФБУН ГНЦ ВБ «Вектор» Адрес: 630559, Новосибирская область, пос. Кольцово Тел.: (383) 336-61-32, факс: (383) 363-74-09

ivankina@vector.nsc.ruNetesovS. V.НетесовС. В.
Russian Federation

доктор биологических наук, профессор, член-кор. РАН, проректор по научной работе Новосибирского национального исследовательского государственного университета Адрес: 630090, Новосибирск, ул. Пирогова, д. 2 Тел.: (383) 330-22-42, факс: (383) 330-32-55

nauka@nsu.ruChumakovP. M.ЧумаковП. М.
Russian Federation

доктор биологических наук, профессор, заведующий лабораторией Института молеку- лярной биологии им. В.А. Энгельгардта РАН Адрес: 119991, Москва, ул. Вавилова, д. 32 Тел.: (926) 769-01-90, факс: (499) 135-14-05

peter@chumakov.comState Research Center of Virology and Biotechnology «Vector», Koltsovo, Novosibirsk Region Institute of Cytology and Genetics of SB RAS, NovosibirskФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор», Новосибирск ФГБУН «Институт цитологии и генетики Сибирского отделения РАН», НовосибирскState Research Center of Virology and Biotechnology «Vector», Koltsovo, Novosibirsk RegionФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор», НовосибирскState Research Center of Virology and Biotechnology «Vector», Koltsovo, Novosibirsk Region Novosibirsk National Research State University, NovosibirskФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор», Новосибирск ФГБОУ ВПО «Новосибирский национальный исследовательский государственный университет»Novosibirsk National Research State University, Novosibirsk Engelhardt Institute of Molecular Biology of RAS, Moscow Lerner Research Institute, Cleveland Clinic Foundation, ClevelandФГБОУ ВПО «Новосибирский национальный исследовательский государственный университет» ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта РАН», Москва Научно-исследовательский институт при клинике Лернера, Кливленд, США22022012672Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук424707082015Copyright ©; 2012, "Paediatrician" Publishers LLCCopyright ©; 2012, Издательство "Педиатръ"2012"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/344

Parvoviruses such as parvovirus H-1 (H-1PV) may selectively infect and lysis cancer cells. The parvoviruses also induce an immune system to eliminate the tumor cells through the formation of anti-cancer immunity. One of the possible mechanisms of antitumor activity is associated with the direct induction of apoptosis by parvoviral proteins NS1 and 11 kDa. Parvovirus-based vectors are promising for gene therapy of oncological diseases and genetic disorders in humans. Parvoviruses were successfully used for the experimental treatment on animal models of human glioma, neuroblastomas, lymphomas, pancreatic carcinoma, carcinomas and breast tumors. ParvOryx is the first oncolytic preparation constructed on the base of H-1PV; its phase I/IIa clinical trials in patients with glioblastoma multiforme are in process.

Парвовирусы, и прежде всего парвовирус H-1 (H-1PV), способны селективно инфицировать и лизировать клетки раковых опухолей. При этом парвовирусы вызывают иммуномодулирующий эффект, приводя к элиминации опухолевых клеток посредством усиления противоракового иммунитета. Один из возможных механизмов противоопухолевого действия связан с прямой индукцией апоптоза белками 11кДа и NS1 парвовирусов. Векторные системы на основе генома парвовирусов также перспективны для генной терапии различных онкологических и генетических заболеваний человека. Парвовирусы были успешно использованы для экспериментального лечения глиомы, нейробластомы, лимфомы, гепатомы, карциномы поджелудочной железы и опухолей молочной железы человека в экспериментах на животных. Первый онколитический препарат ParvOryx на основе парвовируса H-1 проходит клинические испытания фазы I/IIa на пациентах c мультиформной глиобластомой.

parvovirusesoncolytic virusesgliomacancerпарвовирусыонколитические вирусыглиомараковые заболевания1. Maxwell I.H., Terrell K.L., Maxwell F. Autonomous parvovirus vectors. Methods. 2002; 28 (2): 168−181.2. Tattersall P. The evolution of parvoviral taxonomy. In the parvoviruses. ed. J.R. Kerr, M.E. Bloom, R.M. Linden et al. Hodder Arnold: London. 2006. P. 5−14.3. Chow B.D., Esper F.P. The human bocaviruses: a review and discussion of their role in infection. Clin. Lab. Med. 2009; 29 (4): p. 695−713.4. Berns K.I., Parvovirus replication. Microbiol. Rev. 1990; 54 (3): 316−329.5. Rommelaere J., Giese N., Cziepluch C., Cornelis J.J. Parvoviruses as anti-cancer agents. In Viral therapy of human cancers. ed. J.G. Sinkovics, J.C. Horvath. Marcel Dekker: New York. 2005. Р. 627−675.6. Rommelaere J., Cornelis J.J. Antineoplastic activity of parvoviruses. J. Virol. Methods. 1991; 33 (3): 233−251.7. Spalholz B.A., Tattersall P. Interaction of minute virus of mice with differentiated cells: strain-dependent target cell specificity is mediated by intracellular factors. J. Virol. 1983; 46 (3): 937−943.8. Young N.S. Parvovirus infection and its treatment. Clin. Exp. Immunol. 1996; 104 (Suppl. 1): 26−30.9. Deleu L., Pujol A., Faisst S. et al. Activation of promoter P4 of the autonomous parvovirus minute virus of mice at early S phase is required for productive infection. J. Virol. 1999; 73 (5): 3877−3885.10. Di Piazza M., Mader C., Geletneky K. et al. Cytosolic activation of cathepsins mediates parvovirus H-1-induced killing of cisplatin and TRAIL-resistant glioma cells. J Virol. 2007; 81 (8): 4186−4198.11. Nuesch J.P., Rommelaere J. A viral adaptor protein modulating casein kinase II activity induces cytopathic effects in permissive cells. Proc. Natl. Acad. Sci USA. 2007; 104 (30): 12482−12487.12. Cornelis J.J., Deleu L., Koch U. et al. Parvovirus oncosuppression in The parvoviruses. Hodder Arnold: London. 2006. Р. 365−384.13. Chen Y.Q., de Foresta F., Hertoghs J. et al. Selective killing of simian virus 40-transformed human fibroblasts by parvovirus H-1. Cancer Res. 1986; 46 (7): 3574−3579.14. Cornelis J.J., Becquart P., Duponchel N. et al. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice. J. Virol. 1988; 62 (5): 1679−1686.15. Cornelis J.J., Spruyt N., Spegelaere P. et al. Sensitization of transformed rat fibroblasts to killing by parvovirus minute virus of mice correlates with an increase in viral gene expression. J. Virol. 1988; 62 (9): 3438−3444.16. Van Hille B., Duponchel N., Salome N. et al. Limitations to the expression of parvoviral nonstructural proteins may determine the extent of sensitization of EJ-ras-transformed rat cells to minute virus of mice. Virology. 1989; 171 (1): 89−97.17. Guetta E., Mincberg M., Mousset S. et al. Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production. J. Virol. 1990; 64 (1): 458−462.18. Salome N., van Hille B., Duponchel N. et al. Sensitization of transformed rat cells to parvovirus MVMp is restricted to specific oncogenes. Oncogene. 1990; 5 (1): 123−130.19. Mousset S., Ouadrhiri Y., Caillet-Fauquet P. et al. The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression. J. Virol. 1994; 68 (10): 6446−6453.20. Van Pachterbeke C., Tuynder M., Cosyn J.P. et al. Parvovirus H-1 inhibits growth of short-term tumor-derived but not normal mammary tissue cultures. Int. J. Cancer. 1993; 55 (4): 672−677.21. Herrero Y.C.M., Cornelis J.J., Herold-Mende C. et al. Parvovirus H-1 infection of human glioma cells leads to complete viral replication and efficient cell killing. Int. J. Cancer. 2004; 109 (1): 76−84.22. Faisst S., Guittard D., Benner A. et al. Dose-dependent regression of HeLa cell-derived tumours in SCID mice after parvovirus H-1 infection. Int. J. Cancer. 1998; 75 (4): 584−589.23. Ball-Goodrich L.J., Leland S.E., Johnson E.A. et al. Rat parvovirus type 1: the prototype for a new rodent parvovirus serogroup. J. Virol. 1998; 72 (4): 3289−3299.24. McKisic M.D., Paturzo F.X., Smith A.L. Mouse parvovirus infection potentiates rejection of tumor allografts and modulates T-cell effector functions. Transplantation. 1996; 61 (2): 292−299.25. Lacroix J., Leuchs B., Li J. et al. Parvovirus H1 selectively induces cytotoxic effects on human neuroblastoma cells. Int. J. Cancer. 2010; 127 (5): 1230−1239.26. Rommelaere J., Cornelis J.J. Autonomous parvoviruses., in Replication-Competent Viruses for Cancer Therapy. Karger: Basel. 2001. Р. 100−128.27. Randall R.E., Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 2008; 89 (1): 1−47.28. Rommelaere J., Geletneky K., Angelova A.L. et al. Oncolytic parvoviruses as cancer therapeutics. Cytokine Growth Factor Rev. 2010; 21 (2−3): 185−195.29. Cotmore S.F., Tattersall P. The autonomously replicating parvoviruses of vertebrates. Adv. Virus Res. 1987; 33: 91−174.30. Niskanen E.A., Ihalainen T.O., Kalliolinna O. et al. Effect of ATP binding and hydrolysis on dynamics of canine parvovirus NS1. J. Virol. 2010; 84 (10): 5391−5403.31. Chen A.Y., Zhang E.Y., Guan W. et al. The small 11 kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells. Blood. 2010; 115 (5): 1070−1080.32. Moehler M.H., Zeidler M., Wilsberg V. et al. Parvovirus H-1-induced tumor cell death enhances human immune response in vitro via increased phagocytosis, maturation, and cross-presentation by dendritic cells. Hum. Gene Ther. 2005; 16 (8): 996−1005.33. Grekova S.P., Aprahamian M., Daeffler L. et al. Interferon gamma improves the vaccination potential of oncolytic parvovirus H-1PV for the treatment of peritoneal carcinomatosis in pancreatic cancer. Cancer Biol Ther. 2011; 12 (10): 888−895.34. Bhat R., Dempe S., Dinsart C. et al. Enhancement of NK cell antitumor responses using an oncolytic parvovirus. Int. J. Cancer. 2011; 128 (4): 908−919.35. Raykov Z., Grekova S., Galabov A.S. et al. Combined oncolytic and vaccination activities of parvovirus H-1 in a metastatic tumor model. Oncol. Rep. 2007; 17 (6): 1493−1499.36. Jacoby R.O., Ball-Goodrich L.J., Besselsen D.G. et al. Rodent parvovirus infections. Lab. Anim. Sci. 1996; 46 (4): 370−380.37. Hueffer K., Parrish C.R. Parvovirus host range, cell tropism and evolution. Curr. Opin. Microbiol. 2003; 6 (4): 392−398.38. Cotmore S.F., Tattersall P. Parvoviral host range and cell entry mechanisms. Adv. Virus Res. 2007; 70: 183−232.39. Geletneky K., Herrero Y.C.M., Rommelaere J. et al. Oncolytic potential of rodent parvoviruses for cancer therapy in humans: a brief review. J. Vet. Med. B Infect. Dis. Vet. Public Health. 20015; 52 (7−8): 327−330.40. Angelova A.L., Aprahamian M., Balboni G. et al. Oncolytic rat parvovirus H-1PV, a candidate for the treatment of human lymphoma: In vitro and in vivo studies. Mol. Ther. 2009; 17 (7): 1164−1172.41. Angelova A.L., Aprahamian M., Grekova S.P. et al. Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV. Clin. Cancer Res. 2009; 15 (2): 511−519.42. Moehler M., Blechacz B., Weiskopf N. et al. Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors. Cancer Gene Ther. 2001; 8 (3): 158−167.43. Dupressoir T., Vanacker J.M., Cornelis J.J. et al. Inhibition by parvovirus H-1 of the formation of tumors in nude mice and colonies in vitro by transformed human mammary epithelial cells. Cancer Res. 1989; 49 (12): 3203−3208.44. Van Pachterbeke C., Tuynder M., Brandenburger A. et al. Varying sensitivity of human mammary carcinoma cells to the toxic effect of parvovirus H-1. Eur. J. Cancer. 1997; 33 (10): 1648−1653.45. Faisst S., Schlehofer J.R., zur Hausen H. Transformation of human cells by oncogenic viruses supports permissiveness for parvovirus H-1 propagation. J. Virol. 1989; 63 (5): 2152−2158.46. Telerman A., Tuynder M., Dupressoir T. et al. A model for tumor suppression using H-1 parvovirus. Proc. Natl. Acad. Sci U S A. 1993; 90 (18): 8702−8706.47. Rayet B., Lopez-Guerrero J.A., Rommelaere J. et al. Induction of programmed cell death by parvovirus H-1 in U937 cells: connection with the tumor necrosis factor alpha signalling pathway. J. Virol. 1998; 72 (11): 8893−8903.48. Russell S.J., Brandenburger A., Flemming C.L. et al. Transformation-dependent expression of interleukin genes delivered by a recombinant parvovirus. J. Virol. 1992; 66 (5): 2821−2828.49. Ponnazhagan S., Weigel K.A., Raikwar S.P. et al. Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and expression of transduced genes. J. Virol. 1998; 72 (6): 5224−5230.50. Malerba M., Daeffler L., Rommelaere J. et al. Replicating parvoviruses that target colon cancer cells. J. Virol. 2003; 77 (12): 6683−6691.51. Singh P., Destito G., Schneemann A. et al. Canine parvovirus-like particles, a novel nanomaterial for tumor targeting. J. Nanobiotechnology. 2006; 4: 2.52. Wetzel K., Struyf S., Van Damme J. et al. MCP-3 (CCL7) delivered by parvovirus MVMp reduces tumorigenicity of mouse melanoma cells through activation of T lymphocytes and NK cells. Int. J. Cancer. 2007; 120 (6): 1364−1371.53. Enderlin M., Kleinmann E.V., Struyf S. et al. TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. Cancer Gene Ther. 2009; 16 (2): 149−160.54. Palmer G.A., Tattersall P. Autonomous parvoviruses as gene transfer vehicles in Parvoviruses, from Molecular Biology to Pathology and Therapeutic Uses. Karger: Basel. 2000. Р. 178−202.55. Brandenburger A., Coessens E., El Bakkouri K. et al. Influence of sequence and size of DNA on packaging efficiency of parvovirus MVM-based vectors. Hum. Gene Ther. 1999; 10 (7): 1229−1238.56. Brandenburger A., Velu T. Autonomous parvovirus vectors: preventing the generation of wild-type or replication-competent virus. J. Gene Med. 2004; 6 (Suppl. 1): 203−211.57. Kestler J., Neeb B., Struyf S. et al. cis requirements for the efficient production of recombinant DNA vectors based on autonomous parvoviruses. Hum. Gene Ther. 1999; 10 (10): 1619−1632.58. Haag A., Menten P., Van Damme J. et al. Highly efficient transduction and expression of cytokine genes in human tumor cells by means of autonomous parvovirus vectors; generation of antitumor responses in recipient mice. Hum. Gene Ther. 2000; 11 (4): 597−609.59. Dupont F., Avalosse B., Karim A. et al. Tumor-selective gene transduction and cell killing with an oncotropic autonomous parvovirus-based vector. Gene Ther. 2000; 7 (9): 790−796.60. Gancberg D., Zeicher M., Bakkus M. et al. Oncoselective transduction of CD80 and CD86 in tumor cell lines using an autonomous recombinant parvovirus. Anticancer Res. 2000; 20 (3A): 1825−1832.61. Olijslagers S., Dege A.Y., Dinsart C. et al. Potentiation of a recombinant oncolytic parvovirus by expression of Apoptin. Cancer Gene Ther. 2001; 8 (12): 958−965.62. Wetzel K., Menten P., Opdenakker G. et al. Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts. J. Gene Med. 2001; 3 (4): 326−337.63. Giese N.A., Raykov Z., DeMartino L. et al. Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice. Cancer Gene Ther. 2002; 9 (5): 432−442.64. Palmer G.A., Brogdon J.L., Constant S.L. et al. A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation. J. Virol. 2004; 78 (3): 1101−1108.65. Cornelis J.J., Salome N., Dinsart C. et al. Vectors based on autonomous parvoviruses: novel tools to treat cancer? J. Gene Med. 2004; 6 (Suppl. 1): 193−202.66. Kimsey P.B., Engers H.D., Hirt B. et al. Pathogenicity of fibroblast- and lymphocyte-specific variants of minute virus of mice. J. Virol. 1986; 59 (1): 8−13.67. Dupont F., Karim A., Dumon J.C. et al. A novel MVMp-based vector system specifically designed to reduce the risk of replication-competent virus generation by homologous recombination. Gene Ther. 2001; 8 (12): 921−929.68. El Bakkouri K., Servais C., Clement N. et al. In vivo anti-tumour activity of recombinant MVM parvoviral vectors carrying the human interleukin-2 cDNA. J. Gene Med. 2005; 7 (2): 189−197.69. Krieg A.M. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug. Discov. 2006; 5 (6): 471−484.70. Ashkar A.A., Rosenthal K.L. Toll-like receptor 9, CpG DNA and innate immunity. Curr. Mol. Med. 2002; 2 (6): 545−556.71. Dalpke A., Zimmermann S., Heeg K. Immunopharmacology of CpG DNA. Biol. Chem. 2002; 383 (10): 1491−1500.72. Davila E., Velez M.G., Heppelmann C.J. et al. Creating space: an antigen-independent, CpG-induced peripheral expansion of naive and memory T lymphocytes in a full T-cell compartment. Blood. 2002; 100 (7): 2537−2545.73. Raykov Z., Grekova S., Leuchs B. et al. Arming parvoviruses with CpG motifs to improve their oncosuppressive capacity. Int. J. Cancer. 2008; 122 (12): 2880−2884.74. Young S.M., McCarty J.D.M., Degtyareva N. et al. Roles of adeno-associated virus Rep protein and human chromosome 19 in site-specific recombination. J. Virol. 2000; 74 (9): 3953−3966.75. Park K., Kim W.J., Cho Y.H. et al. Cancer gene therapy using adeno-associated virus vectors. Front Biosci. 2008; 13: 2653−2659.76. Ni T.H., McDonald W.F., Zolotukhin I. et al. Cellular proteins required for adeno-associated virus DNA replication in the absence of adenovirus coinfection. J. Virol. 1998; 72 (4): 2777−2787.77. Herzog R.W., Cao O., Srivastava A. Two decades of clinical gene therapy ― success is finally mounting. Discov. Med. 2010; 9 (45): 105−111.