Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug

The problems of oncological disease treatment are considered relevant and timely issues of the current research programs. Since monotherapy is increasingly clear to be less effective than combination therapy, the novel studies seek for advancement of current treatments and development of new ones em...

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Autores principales: T. V. Bauer, T. V. Tregubchak, S. N. Shchelkunov, R. A. Maksyutov, E. V. Gavrilova
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Publicado: SPb RAACI 2020
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spelling oai:doaj.org-article:5ae29a537c5e4cbda7a097131bc4b54b2021-11-18T08:03:48ZObtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug1563-06252313-741X10.15789/1563-0625-OVV-1594https://doaj.org/article/5ae29a537c5e4cbda7a097131bc4b54b2020-04-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1594https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThe problems of oncological disease treatment are considered relevant and timely issues of the current research programs. Since monotherapy is increasingly clear to be less effective than combination therapy, the novel studies seek for advancement of current treatments and development of new ones employing oncolytic immunotherapy being among the most rapidly evolving approaches. Modern genetic engineering techniques enable new applications of oncolytic viruses in the frames of combined cancer therapy. These applications are feasible, due to the abilities of oncolytic viruses to destruct tumor cells, like as by changing susceptibility of cancer cells to anti-tumor drug, and upon the whole body, thus overcoming the mechanisms conferring immunoresistance of tumor cells. In the present work, we have developed a recombinant vaccinia virus which is a promising platform for designing the antitumor drugs. The following modifications of viral genome were made by means of genetic engineering: gene encoding granulocyte-macrophage colony-stimulating factor was inserted into the region of viral thymidine kinase gene; viral A34R gene encoding a membrane glycoprotein, was replaced by A34R gene with two nucleotide substitutions resulting into D110N and K151E mutations which cause increased proportion of extracellular enveloped virions during the virus reproduction. Some properties of the recombinant virus were studied in vitro. The virus was shown to produce granulocyte-macrophage colony stimulating factor, and high numbers of extracellular enveloped virions. The genome modifications had no effect upon viral replication.T. V. BauerT. V. TregubchakS. N. ShchelkunovR. A. MaksyutovE. V. GavrilovaSPb RAACIarticlevaccinia virusextracellular envelope formcanceroncolytic virusimmunotherapygranulocyte-macrophage colony-stimulating factorImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 2, Pp 371-378 (2020)
institution DOAJ
collection DOAJ
language RU
topic vaccinia virus
extracellular envelope form
cancer
oncolytic virus
immunotherapy
granulocyte-macrophage colony-stimulating factor
Immunologic diseases. Allergy
RC581-607
spellingShingle vaccinia virus
extracellular envelope form
cancer
oncolytic virus
immunotherapy
granulocyte-macrophage colony-stimulating factor
Immunologic diseases. Allergy
RC581-607
T. V. Bauer
T. V. Tregubchak
S. N. Shchelkunov
R. A. Maksyutov
E. V. Gavrilova
Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
description The problems of oncological disease treatment are considered relevant and timely issues of the current research programs. Since monotherapy is increasingly clear to be less effective than combination therapy, the novel studies seek for advancement of current treatments and development of new ones employing oncolytic immunotherapy being among the most rapidly evolving approaches. Modern genetic engineering techniques enable new applications of oncolytic viruses in the frames of combined cancer therapy. These applications are feasible, due to the abilities of oncolytic viruses to destruct tumor cells, like as by changing susceptibility of cancer cells to anti-tumor drug, and upon the whole body, thus overcoming the mechanisms conferring immunoresistance of tumor cells. In the present work, we have developed a recombinant vaccinia virus which is a promising platform for designing the antitumor drugs. The following modifications of viral genome were made by means of genetic engineering: gene encoding granulocyte-macrophage colony-stimulating factor was inserted into the region of viral thymidine kinase gene; viral A34R gene encoding a membrane glycoprotein, was replaced by A34R gene with two nucleotide substitutions resulting into D110N and K151E mutations which cause increased proportion of extracellular enveloped virions during the virus reproduction. Some properties of the recombinant virus were studied in vitro. The virus was shown to produce granulocyte-macrophage colony stimulating factor, and high numbers of extracellular enveloped virions. The genome modifications had no effect upon viral replication.
format article
author T. V. Bauer
T. V. Tregubchak
S. N. Shchelkunov
R. A. Maksyutov
E. V. Gavrilova
author_facet T. V. Bauer
T. V. Tregubchak
S. N. Shchelkunov
R. A. Maksyutov
E. V. Gavrilova
author_sort T. V. Bauer
title Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
title_short Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
title_full Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
title_fullStr Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
title_full_unstemmed Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug
title_sort obtainingvaccinia virus with increased production of extracellular enveloped virions and directing gm-csf synthesis as a promising basis for development of antitumor drug
publisher SPb RAACI
publishDate 2020
url https://doaj.org/article/5ae29a537c5e4cbda7a097131bc4b54b
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AT tvtregubchak obtainingvacciniaviruswithincreasedproductionofextracellularenvelopedvirionsanddirectinggmcsfsynthesisasapromisingbasisfordevelopmentofantitumordrug
AT snshchelkunov obtainingvacciniaviruswithincreasedproductionofextracellularenvelopedvirionsanddirectinggmcsfsynthesisasapromisingbasisfordevelopmentofantitumordrug
AT ramaksyutov obtainingvacciniaviruswithincreasedproductionofextracellularenvelopedvirionsanddirectinggmcsfsynthesisasapromisingbasisfordevelopmentofantitumordrug
AT evgavrilova obtainingvacciniaviruswithincreasedproductionofextracellularenvelopedvirionsanddirectinggmcsfsynthesisasapromisingbasisfordevelopmentofantitumordrug
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