Recombinant avian adenovirus CELO expressing the human interleukin-2: characterization in vitro, in ovo and in vivo

Черенова, Л. В.; Logunov, Denis Y.; Shashkova, Elena V.; Шмаров, М. М.; Verkhovskaya, L. V.; Neugodova, Galina L.; Kazansky, Dmitry; Doronin, Konstantin; Naroditsky, Boris S.

doi:10.1016/j.virusres.2003.11.018

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…The construction of CELO-GFP was described previously. 16 The first-generation Ad5-based vectors Ad5-EGFP and Ad5-TK were constructed by cotransfection of 293 cells with pRW11 or pRW215 shuttle plasmids, respectively, and pJM17 (Microbix Biosystems). These Ad5-based vectors have the E1 region deleted and carry the expression cassette at the site of the deletion.…”

Section: Adenovirus Vectorsmentioning

confidence: 99%

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

et al. 2005

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Avian adenovirus CELO is a novel adenovirus vector system with the advantages of efficient production, high virion stability, and the absence of crossreactivity with Ad5-neutralizing antibodies. In this study, we evaluated the anticancer efficacy of a CELO vector encoding the herpes simplex virus type 1 thymidine kinase, a prodrug-activating therapeutic gene. Vectors carrying the gene for HSV-tk or EGFP under the control of the HCMV promoter in place of the ''nonessential'' region of the CELO genome were constructed. Anticancer activity of the CELO-TK vector was studied in vitro, in human and murine tumor cells in cell culture, and in vivo, in established subcutaneous murine B16 melanoma tumors in C57BL/6 mice. The CELO-TK vector mediated delivery of functional HSV-tk to tumor cell lines in cell culture. Comparison of the CELO-TK vector to a first-generation human adenovirus type 5 vector Ad5-TK in cultured H1299 cells showed equal levels of functional activity at increasing multiplicities of infection with CELO-based vector. CELO vectors allowed for transduction and expression of EGFP and HSV-tk genes in subcutaneous melanoma tumors in C57BL/6 mice. Intratumoral injections of CELO-TK followed by ganciclovir administration resulted in suppression of tumor growth and significantly increased the median of survival. The results of the study demonstrated the efficacy of CELO vector as a vehicle for the delivery of prodrug-activating genes such as HSV-tk to tumor cells in vitro and in vivo. Cancer Gene Therapy ( 1 This experimental approach to cancer treatment is currently in a transition from promise to reality with recent approval of an adenovirus (Ad) vector expressing p53 for use in clinics and with many more vectors in late stages of clinical trials.2 At the same time, new generations of cancer gene therapy vectors are being developed that will provide higher levels of efficacy, specificity, and cost-effectiveness.Whereas human Ad type 5 (Ad5) is a common platform for Ad vectors for the in vitro and in vivo delivery of genes, 3,4 non-human adenoviruses (Ads), also referred to as ''xenogeneic'' vectors, are currently emerging as alternative or additional gene delivery vehicles. 5,6 Avian Ad CELO (FAV-1) is a novel non-human Ad vector that has potential advantages for the development of anticancer vectors including: (i) the absence of pre-existing immunity to CELO in the human population, 7 (ii) the absence of immunological crossreactivity between virions of Ad5 and CELO, 8 which allows for in vivo transduction by CELO vectors in the presence of anti-Ad5 neutralizing antibodies, 9 (iii) higher stability of CELO virions as compared to Ad5 virions, 7 (iv) the natural inability of CELO to replicate in non-avian cells, which renders CELO vectors gene delivery vehicles rather than replicative agents in mammalian cells, 7 (v) the ability of CELO vectors to grow in noncomplementing cells resulting in the absence of recombination with the homologous viral DNA sequences in the genome of a complementing cell line, and the a...

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Section: Adenovirus Vectorsmentioning

confidence: 99%

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

et al. 2005

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“…In poultry, fowl adenovirus (FAdV) has been used to express a number of complex viral antigens (Sheppard et al, 1998;Johnson et al, 2003;Francois et al, 2004) and eukaryotic proteins including chicken interferon-g (Rauw et al, 2007), interleukin-2 (Cherenova et al, 2004) and thymidine kinase (Shashkova et al, 2005). These reports suggest that FAdV could be used as an effective delivery vector for complex eukaryotic proteins such as antibody fragments, with the added potential for prolonged in vivo release due to the replicative ability of the virus.…”

Section: Introductionmentioning

confidence: 99%

Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus

et al. 2010

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Single-chain variable fragments (scFv) contain the heavy and light chain variable domains of immunoglobulin, joined by a short peptide linker. Previously, our laboratory has produced neutralizing scFv to epitopes of infectious bursal disease virus (IBDV). The in vitro delivery and expression of one of these scFv with and without the C H 2-C H 4 Fc domain of chicken IgY attached (scFv-Fc) by a serotype 8 fowl adenovirus (FAdV-8) vector was investigated in the present study. A panel of FAdV-8 vectors was constructed, each containing a different transgene (scFv or scFv-Fc), a different promoter to drive scFv and scFv-Fc transcription (CMVie or the fowl adenovirus major late promoter), and a different sized, right-hand end genomic deletion (52 bp or 2.3 kb). This panel was used to establish what effect these variables had on protein production, viral replication and scFv transcription, as measured by enzyme-linked imunosorbent assay and real-time polymerase chain reaction. Our results showed that, using a FAdV-8 vector containing the optimal CMVie promoter/2.3 kb deletion combination, we successfully expressed a secreted form of both scFv and scFv-Fc that were able to neutralize IBDV both in vitro and in ovo. These studies indicate that the FAdV-8 vector may be a promising candidate to deliver and express therapeutic molecules such as scFv and scFv-Fc in vivo in poultry.

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“…4,5 To avoid pre-existing humoral immunity in patients, several groups have investigated adenovirus serotypes from alternative species such as cows, [6][7][8][9][10][11][12][13][14] sheep, [15][16][17][18][19][20][21][22][23][24][25] chimpanzees, [26][27][28] dogs [29][30][31][32][33][34][35][36] and chickens. [37][38][39][40] Chicken embryo lethal orphan virus (CELO; fowl adenovirus type 1), characterized as an infectious agent in 1957, 41 is attractive as a gene delivery vector since it is simple and cheap to produce in bulk in chicken embryos and has a good safety profile being completely replication defective in human cells, even in the presence of wild-type human adenovirus. 42 CELO is structurally similar to mammalian adenoviruses possessing an icosahedral capsid of 70-80 nm composed of hexon and penton proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Fibre 1 is 42.5 nm in length and contains a sharp kink, while fibre 2 is 8.5 nm in length and straight. [42][43][44][45] Although recombinant CELO has been demonstrated to transduce a range of mammalian cell lines and primary cells, [37][38][39][40] in general, the level of transgene expression falls below that of adenovirus type 5 (Ad5) vectors when delivered at comparable multiplicity of infection.…”

Section: Introductionmentioning

confidence: 99%

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells

et al. 2005

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Recombinant avian adenovirus CELO expressing the human interleukin-2: characterization in vitro, in ovo and in vivo

Cited by 13 publications

References 23 publications

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells

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