Apoptin enhances the oncolytic activity of vaccinia virus in vitro

Кочнева, Г. В.; Бабкина, И. Н.; Лупан, Т. А.; Гражданцева, А. А.; Yudin, P. V.; Сиволобова, Г. Ф.; Shvalov, Аlexander N.; Popov, Evgeniy; Бабкин, И. В.; Нетесов, С. В.; Chumakov, P. M.

doi:10.1134/s0026893313050075

Cited by 16 publications

(20 citation statements)

References 24 publications

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“…This method has been shown to be highly efficient for the construction of recombinant VACVs coding the apoptosis-inducing protein apoptin [30]. The scheme used to engineer the recombinant VV-GMCSF-Lact is illustrated in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

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Engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy

et al. 2016

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Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes. Cell culture experiments revealed that engineered VV-GMCSF-Lact induced the death of cultured cancer cells more efficiently than recombinant VACV coding only GM-CSF (VV-GMCSF-dGF). Normal human MCF-10A cells were resistant to both recombinants up to 10 PFU/cell. The selectivity index for breast cancer cells measured in pair cultures MCF-7/MCF-10A was 200 for recombinant VV-GMCSF-Lact coding lactaptin and 100 for VV-GMCSF-dGF. Using flow cytometry we demonstrated that both recombinants induced apoptosis in treated cells but that the rate in the cells with active caspase −3 and −7 was higher after treatment with VV-GMCSF-Lact than with VV-GMCSF-dGF. Tumor growth inhibition and survival outcomes after VV-GMCSF-Lact treatment were estimated using immunodeficient and immunocompetent mice models. We observed that VV-GMCSF-Lact efficiently delays the growth of sensitive and chemoresistant tumors. These results demonstrate that recombinant VACVs coding an apoptosis-inducing protein have good therapeutic potential against chemoresistant tumors. Our data will also stimulate further investigation of coding lactaptin double recombinant VACV in clinical settings.

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Section: Resultsmentioning

confidence: 99%

“…Parental and recombinant viruses were grown in a monolayer of CV-1 cells and purified as described previously [30]. The VV-GMCSF-S1/3 strain contains an insert of cDNA sequence encoding human GM-CSF (GenBank Acc.M11220.1) in the central part of the virus tk gene between nucleotides 81277 and 81308 (GenBank Acc.…”

Section: Methodsmentioning

confidence: 99%

Engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy

et al. 2016

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“…A significant advantage of the use of baculovirus is the lack of preexisting immunity [194]. Moreover, apoptin also enhances the oncolytic property of Newcastle disease virus (NDV), vaccinia virus and H-1 parvovirus [195][196][197][198]. NDV expressing apoptin (rNDV-apoptin) showed enhanced efficacy in suppressing tumor growth in mice bearing A549-induced tumors without affecting normal cells [197].…”

Section: Apoptinmentioning

confidence: 99%

Viral genes as oncolytic agents for cancer therapy

Gupta

Gandham

Sahoo

et al. 2014

Cell. Mol. Life Sci.

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Many viruses have the ability to modulate the apoptosis, and to accomplish it; viruses encode proteins which specifically interact with the cellular signaling pathways. While some viruses encode proteins, which inhibit the apoptosis or death of the infected cells, there are viruses whose encoded proteins can kill the infected cells by multiple mechanisms, including apoptosis. A particular class of these viruses has specific gene(s) in their genomes which, upon ectopic expression, can kill the tumor cells selectively without affecting the normal cells. These genes and their encoded products have demonstrated great potential to be developed as novel anticancer therapeutic agents which can specifically target and kill the cancer cells leaving the normal cells unharmed. In this review, we will discuss about the viral genes having specific cancer cell killing properties, what is known about their functioning, signaling pathways and their therapeutic applications as anticancer agents.

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“…It possesses a unique set of advantages, including the natural tropism for tumor cells, the ability to infect a wide spectrum of cells, rapid and exclusively cytoplasmic replication, and the large genome suitable for the insertion of multiple foreign genes [ 22 , 23 ]. We constructed an apoptin-producing recombinant VACV based on the L-IVP strain [ 1 ]. In the construct the apoptin gene replaces a part of the C11R gene that encodes the viral growth factor (VGF).…”

Section: Introductionmentioning

confidence: 99%

“…The deletion of the VGF gene provides an additional attenuation of the virus [ 24 ]. The obtained VACV recombinant VVdGF-ApoS24/2 effectively expresses apoptin in the infected cells, and demonstrates a significantly enhanced selective lysis of the human cancer cell lines A549, A431, U87MG, RD and MCF-7 in vitro, as compared with the parental virus strain L-IVP and its variant VVdGF2/6 with the deletion of the C11R gene [ 1 ]. The present study aims the assessment of oncolytic properties of the apoptin-producing recombinant VACV (VVdGF-ApoS24/2) in the model of nude mice xenografts of the human A431 epithelioid carcinoma cells, in comparison with the parental L-IVP virus strain.…”

Section: Introductionmentioning

confidence: 99%

Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression

et al. 2014

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A recombinant vaccinia virus VVdGF-ApoS24/2 expressing apoptin selectively kills human cancer cells in vitro [Kochneva et al., 2013]. We compared the oncolytic activity of this recombinant with that of the parental strain L-IVP using a model of human A431 carcinoma xenografts in nude mice. Single intratumoral injections (2×107 PFU/mouse) of the viruses produced a dramatic decrease in tumor volumes, which was higher after injection of apoptin-producing virus. The tumor dried out after the injection of recombinant while injection of L-IVP strain resulted in formation of cavities filled with cell debris and liquid. Both viruses rapidly spread in xenografts and replicate exclusively in tumor cells causing their destruction within 8 days. Both viruses induced insignificant level of apoptosis in tumors. Unlike the previously described nuclear localization of apoptin in cancer cells the apoptin produced by recombinant virus was localized to the cytoplasm. The apoptin did not induce a typical apoptosis, but it rather influenced pathway of cell death and thereby caused tumor shrinkage. The replacement of destroyed cells by filamentous material is the main feature of tumor regression caused by the VVdGF-ApoS24/2 virus. The study points the presence of complicated mechanisms of apoptin effects at the background of vaccinia virus replication.

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Apoptin enhances the oncolytic activity of vaccinia virus in vitro

Cited by 16 publications

References 24 publications

Engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy

Engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy

Viral genes as oncolytic agents for cancer therapy

Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression

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