Adenovirus Mediated Alpha Interferon (IFN‐α) Gene Transfer into CD34<sup>+</sup>Cells and CML Mononuclear Cells

Feldman, Eric J.; Ahmed, Tauseef; Lutton, John D.; Farley, Timothy J.; Tani, Kenzaburo; Freund, Mathias; Asano, Shigetaka; Abraham, Nader G.

doi:10.1002/stem.150386

Cited by 23 publications

(13 citation statements)

References 53 publications

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“…However, stem cells are resistant to adenovirus infection. Even with a very high dose of an adenoviral vector and prolonged cell-vector contact, only a limited percentage of stem cells became infected (Watanabe et al, 1996;Feldman et al, 1997;Gu et al, 2002). In addition, we have shown that the hTERT promoter is much less active in CD34 + hematopoietic progenitor cells which is enriched in stem cells than in cancer cells (Gu et al, 2002).…”

Section: Discussionmentioning

confidence: 88%

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

Zhang

Huang

et al. 2002

Oncogene

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Using a binary adenoviral system, we recently showed that the human telomerase reverse transcriptase (hTERT) promoter induces tumor-specific Bax gene expression. However, the strong cytotoxicity of Bax and other pro-apoptotic genes to packaging 293 cells has so far hindered construction of the desired single adenoviral vectors expressing toxic genes. We report here the construction of a single bicistronic adenoviral vector for tumor-specific Bax expression. The vector (Ad/gBax) utilizes the Tet-Off system and expresses a GFP/Bax fusion protein for easy detection. The hTERT promoter drives the expression of tTA, a transactivator capable of binding to TRE (tetracycline-responsive element) in the absence of tetracycline, which in turn induces expression of the GFP-Bax gene. The addition of tetracycline in 293 cells blocks the binding of tTA to TRE and substantially inhibits GFP -Bax expression and toxicity, thus allowing the packaging and production of Ad/gBax. Our data show that Ad/gBax could drive the high expression of GFP -Bax in tumor cells but not in normal cells and mouse tissues. Furthermore, the expression of GFP -Bax fusion protein elicited tumorspecific apoptosis in a variety of human cancer cells in vitro and in vivo at a level comparable to that induced by the binary system. Thus, Ad/gBax may become a potent therapeutic agent for the treatment of cancers.

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Section: Discussionmentioning

confidence: 88%

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

Zhang

Huang

et al. 2002

Oncogene

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“…Although relatively high doses of recombinant adenovirus vectors are required to infect hematopoietic stem cells or embryonic stem cells (43)(44)(45), it has been reported that successful IFN-␣ gene transfection into human CD34 ϩ hematopoietic stem cells was achieved by infection with Ad-CMV/INF-␣ at an MOI of 120 -240 pfu/cell (43,44). In our study, the fluorescent population of embryonic stem cells reached 45.93% 36 h after infection with Ad-CMV/GFP at an MOI of 100 pfu/cell (Fig.…”

Section: Discussionmentioning

confidence: 99%

Development of a Cancer-Targeted Tissue-Specific Promoter System

et al. 2004

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Present cancer gene therapy using proapoptotic genes has had limited success because the therapy is prone to cause side effects as a result of the lack of tissue and cancer specificity. To target cancer cells without damaging normal cells, we have designed a novel dual promoter system in which a tissue-specific transcription system under the control of a cancerspecific promoter drives expression of a therapeutic gene. The applicability of this system was demonstrated by adapting it to target lung cancer. We termed this lung cancer system TTS (TTF1 gene under the control of human telomerase reverse transcriptase promoter and human surfactant protein A1 promoter). The TTS system showed much higher promoter activity in lung cancer cells compared with other kinds of cancer and normal lung cells, including stem cells. Moreover, insertion of negative glucocorticoid responsive elements in the system allows it to be drug controllable. The approaches that we have used could be adapted to target other types of cancer. We report a novel cancer-targeted tissue-specific dual promoter system designed for gene therapy.

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“…This observation is consistent with a report that even a very high dose of an adenoviral vector and prolonged cell-vector contact can infect only a limited percentage of stem cells. 18,19 Nevertheless, in the presence of Superfect and a very high dosage of virus (10 000 MOI), when fluorescent (ie infected) population can reach 60% by Ad/GFP infection (data not shown), transgene expression from the hTERT promoter in human CD34…”

mentioning

confidence: 94%

hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity

Andreeff

Roth

et al. 2002

Gene Ther

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Adenovirus Mediated Alpha Interferon (IFN‐α) Gene Transfer into CD34⁺Cells and CML Mononuclear Cells

Abstract: ABSTRACT

Cited by 23 publications

References 53 publications

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

Development of a Cancer-Targeted Tissue-Specific Promoter System

hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity

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Adenovirus Mediated Alpha Interferon (IFN‐α) Gene Transfer into CD34+Cells and CML Mononuclear Cells

Abstract: ABSTRACT

Cited by 23 publications

References 53 publications

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

A novel single tetracycline-regulative adenoviral vector for tumor-specific Bax gene expression and cell killing in vitro and in vivo

Development of a Cancer-Targeted Tissue-Specific Promoter System

hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity

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Product

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Adenovirus Mediated Alpha Interferon (IFN‐α) Gene Transfer into CD34⁺Cells and CML Mononuclear Cells