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RU2351361C2 - Novel application of adenovirus and nuclear acids encoding it - Google Patents

Novel application of adenovirus and nuclear acids encoding it Download PDF

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Publication number
RU2351361C2
RU2351361C2 RU2004138095/13A RU2004138095A RU2351361C2 RU 2351361 C2 RU2351361 C2 RU 2351361C2 RU 2004138095/13 A RU2004138095/13 A RU 2004138095/13A RU 2004138095 A RU2004138095 A RU 2004138095A RU 2351361 C2 RU2351361 C2 RU 2351361C2
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use according
cells
virus
tumor
nucleus
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RU2004138095/13A
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Russian (ru)
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RU2004138095A (en
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Пер Сонне ХОЛЬМ (DE)
Пер Сонне ХОЛЬМ
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Пер Сонне ХОЛЬМ
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Abstract

FIELD: medicine.
SUBSTANCE: claimed invention relates to field of molecular biology, virology and medicine. Claimed is application of adenovirus for manufacturing medication for tumor treatment. Said virus is replication-deficient in cells which do not contain YB-1 in nucleus and encodes oncogenic protein E1A, which transactivates at least one viral gene from group including E1B55kDa, E4orf6, E4orf6 and E3ADP.
EFFECT: invention can be used for treating tumors demonstrating resistance to many cytostatic medications.
19 cl, 19 dwg, 13 ex

Description

Текст описания приведен в факсимильном виде.

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The text of the description is given in facsimile form.
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Claims (21)

1. Применение вируса для изготовления лекарственного средства для лечения опухолей, отличающееся тем, что указанный вирус представляет собой аденовирус, являющийся дефицитным по репликации в клетках, не содержащих YB-1 в ядре, где указанный вирус кодирует онкогенный белок Е1А, который трансактивирует, по крайней мере, один вирусный ген, где указанный ген выбран из группы, включающей E1B55kDa, E4orf6, E4orf3 и E3ADP.1. The use of a virus for the manufacture of a medicament for the treatment of tumors, characterized in that the virus is an adenovirus that is deficient in replication in cells that do not contain YB-1 in the nucleus, where the virus encodes an oncogenic protein E1A that transactivates at least at least one viral gene, where the specified gene is selected from the group comprising E1B55kDa, E4orf6, E4orf3 and E3ADP. 2. Применение по по п.1, отличающееся тем, что указанный вирус реплицируется в клетках, содержащих YB-1 в ядре.2. The use according to claim 1, characterized in that the virus is replicated in cells containing YB-1 in the nucleus. 3. Применение по п.1, отличающееся тем, что указанным вирусным онкогенным белком является Е1А, и/или указанным онкогеном является ген, кодирующий Е1А, и/или указанным онкогенным белком является Е1А.3. The use according to claim 1, characterized in that said viral oncogenic protein is E1A, and / or said oncogen is a gene encoding E1A, and / or said oncogenic protein is E1A. 4. Применение по п.3, отличающееся тем, что указанный вирусный онкопротеин Е1А не индуцирует ядерную локализацию YB-1.4. The use according to claim 3, characterized in that said viral oncoprotein E1A does not induce nuclear localization of YB-1. 5. Применение по п.1, отличающееся тем, что указанные клетки являются Rb-негативными, и такие клетки являются позитивными по ядерному YB-1, а предпочтительно, указанные клетки являются позитивными по ядерному YB-1 независимо от клеточного цикла.5. The use according to claim 1, characterized in that said cells are Rb-negative and such cells are nuclear YB-1 positive, and preferably, these cells are nuclear YB-1 positive regardless of the cell cycle. 6. Применение по п.1, отличающееся тем, что указанные клетки, образующие опухоль или ее части, являются резистентными к фармакологически эффективным агентам.6. The use according to claim 1, characterized in that said cells forming a tumor or its parts are resistant to pharmacologically effective agents. 7. Применение по п.6, отличающееся тем, что указанные клетки обнаруживают сверхэкспрессию мембрано-связанного транспортного белка Р-гликопротеина.7. The use according to claim 6, characterized in that said cells exhibit overexpression of the membrane-bound transport protein P-glycoprotein. 8. Применение по п.1, отличающееся тем, что указанный вирусный онкогенный белок находится под контролем тканеспецифического и/или опухолеспецифического промотора.8. The use according to claim 1, characterized in that said viral oncogenic protein is under the control of a tissue-specific and / or tumor-specific promoter. 9. Применение по п.1, отличающееся тем, что указанный вирус кодирует YB-1.9. The use according to claim 1, characterized in that the virus encodes YB-1. 10. Применение по п.9, отличающееся тем, что указанный YB-1 находится под контролем тканеспецифического и/или опухолеспецифического промотора.10. The use according to claim 9, characterized in that said YB-1 is under the control of a tissue-specific and / or tumor-specific promoter. 11. Применение по п.1, отличающееся тем, что указанный вирус кодирует, по крайней мере, один белок, выбранный из группы, включающей E4orf6, E4orf3, E1B55kDa и аденовирусный белок E3ADP.11. The use according to claim 1, characterized in that the virus encodes at least one protein selected from the group consisting of E4orf6, E4orf3, E1B55kDa and adenovirus protein E3ADP. 12. Применение по п.1, отличающееся тем, что указанные клетки, образующие опухоль или ее часть, содержат YB-1 в ядре.12. The use according to claim 1, characterized in that said cells forming a tumor or part thereof contain YB-1 in the nucleus. 13. Применение по п.1, отличающееся тем, что указанная опухоль содержит YB-1 в клеточном ядре после индуцирования транспорта YB-1 в это ядро.13. The use according to claim 1, characterized in that said tumor contains YB-1 in the cell nucleus after inducing transport of YB-1 into this nucleus. 14. Применение по п.1, отличающееся тем, что указанный вирус выбран из группы, включающей AdΔ24, dl922-947, E1Δd/01/07, d11119/1131, CB016, dl520 и вирусы, у которых экспрессируемый вирусный онкоген не способен связываться с функциональным генным продуктом - суппрессором опухоли, Rb.14. The use according to claim 1, characterized in that said virus is selected from the group consisting of AdΔ24, dl922-947, E1Δd / 01/07, d11119 / 1131, CB016, dl520 and viruses in which the expressed viral oncogen is not able to bind functional gene product - tumor suppressor, Rb. 15. Применение нуклеиновой кислоты, кодирующей вирус, применяемый по любому из пп.1-14, для изготовления лекарственного средства, а предпочтительно, для изготовления лекарственного средства для лечения опухолей.15. The use of a nucleic acid encoding a virus used according to any one of claims 1 to 14, for the manufacture of a medicinal product, and preferably, for the manufacture of a medicinal product for the treatment of tumors. 16. Применение по п.15, отличающееся тем, что указанные клетки, образующие опухоль или ее части, являются резистентными к фармакологически эффективным агентам.16. The application of clause 15, wherein said cells forming the tumor or parts thereof are resistant to pharmacologically effective agents. 17. Применение по п.16, отличающееся тем, что указанной резистентностью является полирезистентность.17. The application of clause 16, wherein the specified resistance is polyresistance. 18. Применение по п.16 или 17, отличающееся тем, что указанным фармакологически активным агентом является противоопухолевый агент.18. The use according to clause 16 or 17, characterized in that said pharmacologically active agent is an antitumor agent. 19. Применение по п.18, отличающееся тем, что указанным противоопухолевым агентом является цитостатическое средство.
Приоритет по пунктам:19. The use according to claim 18, characterized in that said antitumor agent is a cytostatic agent.
Priority on points: 27.05.2002 по пп.2 - 19;05/27/2002 according to claims 2-19; 19.05.2003 по п.1. 05/19/2003 according to claim 1.
RU2004138095/13A 2002-05-27 2003-05-27 Novel application of adenovirus and nuclear acids encoding it RU2351361C2 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
DE2002123534 DE10223534A1 (en) 2002-05-27 2002-05-27 Use of viruses containing oncogenes for treating tumors, can replicate only in cells having YB-1 transcription factor in the nucleus, also new viral oncogene proteins
DE10223534.1 2002-05-27
DE10225400.1 2002-06-07
DE10225400 2002-06-07
DE10248039.7 2002-10-15
DE10322530 2003-05-19
DE10322530.7 2003-05-19

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RU2351361C2 true RU2351361C2 (en) 2009-04-10

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2337973B8 (en) * 2008-05-16 2011-07-21 Proyecto De Biomedicina Cima, S.L. ADENOVIRUS AUXILIARY SELF-INACTIVANTS FOR THE PRODUCTION OF ADENOVIRUS RECOMBINANTS OF HIGH CAPACITY.

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0931830B1 (en) * 1993-02-16 2001-03-07 Onyx Pharmaceuticals, Inc. Cytopathic viruses for therapy and phophylaxis of neoplasia

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0931830B1 (en) * 1993-02-16 2001-03-07 Onyx Pharmaceuticals, Inc. Cytopathic viruses for therapy and phophylaxis of neoplasia

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HEISE C., HERMISTON Т., 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 Oct; 6(10):1134-9. Erratum in: Nat Med 2000 Dec; 6(12):1412. WONG H.K., ZIFF E.B. Complementary functions of E1a conserved region 1 cooperate with conserved region 3 to activate adenovirus serotype 5 early promoters. J Virol. 1994 Aug; 68(8):4910-20. GANLY.I., KIM Y.T., HANN В., BALMAIN A., BROWN R. Replication and cytolysis of an E1B-attenuated adenovirus in drug-resistant ovarian tumour cells is associated with reduced apoptosis. Gene Ther. 2001 Mar; 8(5):369-75. *
HOLM P.S., BERGMANN К., JURCHOTT К., LAGE H., BRAND К., LADHOFF A., MANTWILL К., CURIEL D.T., DOBBELSTEIN M., DIETEL М., GANSBACHER В., ROYER H.D. YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter. J Biol Chem. 2002 Mar 22; 277(12):10427-34. Epub 2002 Jan 11. *

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