Recent developments in the use of adenoviruses and immunotoxins in cancer gene therapy

Yang, Zheng; Hf, Wang; Zhao, Jing; Yy, Peng; Wang, J; Guinn, Barbara; Lq, Huang

doi:10.1038/sj.cgt.7701054

Cited by 130 publications

(86 citation statements)

References 139 publications

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“…30,31 Specific expression of recombinant active caspase-3 under the control of SLPI promoter for the specific induction of apoptosis is a new attempt for targeted gene therapy in laryngeal carcinoma. With regards to better therapeutic efficacy, the selection/combined use of more potent therapeutic genes, as well as a suitable strategy for comprehensive therapy, are worthy of investigation in our futher work.…”

Section: Discussionmentioning

confidence: 99%

Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

et al. 2012

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The purpose of this study is to develop a specific and efficient targeted gene therapy candidate approach for laryngeal carcinomas. Several promoters of human squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest efficiency and specificity, and was used to control the expression of a recombinant active caspases-3 (revCasp3), which could trigger apoptosis without activation of its upstream cascade elements once expressed in a cell, in an adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase-3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth without obvious loss of body weight and obvious hepatic toxicity. In summary, our study showed the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene therapy for laryngeal squamous cell carcinoma, which needs further systematic investigation.

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Section: Discussionmentioning

confidence: 99%

Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

et al. 2012

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“…Adenoviral vectors have been extensively utilized in gene therapy approaches and offer a number of advantages including the ability to infect a large array of human tissue (both dividing and non-dividing cells), the ease of production of high-titer replication-deficient virus and epichromosomal expression of transgenes. 16,17 Our experiments demonstrate that infection with Ad-Rybp is cytotoxic to a variety of tumor cell types, while sparing normal cell types. Ad-Rybp infection inhibits cell growth by the induction of apoptosis and sensitizes tumor cells to the cytotoxic effect of tumor necrosis factor-a (TNF-a) and etoposide.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

Novak

Phillips

2008

Cancer Gene Ther

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Previous work demonstrated that exogenous expression of Rybp (Ring 1 YY1-binding protein or DEDAF) kills tumor but not nontransformed cells. This tumor-preferential killing activity could be exploited in a gene therapy approach to treat cancer. To test the potential of viral-mediated delivery of Rybp as an anticancer treatment, we generated an adenovirus expressing Rybp (Ad-Rybp). Infection with Ad-Rybp inhibits the proliferation of a range of tumor cell lines, but has no effect on normal cell types. This inhibition of proliferation is the result of the induction of apoptosis, consistent with reports that Rybp regulates apoptosis. Combined Ad-Rybp infection and etoposide treatment resulted in an additive cytotoxic effect in the osteosarcoma cell line U20S. Furthermore, Ad-Rybp infection synergistically cooperates with the death receptor ligand, tumor necrosis factor-a, in the induction of apoptosis. These results suggest that Ad-Rybp may have clinical applicability, either alone or in combination with other agents for the treatment of cancer.

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“…These vectors are valuable particularly for transgene expression in hard-to-transfect cells and have been used widely for the expression of transgenes under both clinical and experimental conditions. 39,40 In recent years, Gendicine and H101, two adenovirus-based bio-drug have been approved by SFDA for the treatment of late stage refractory carcinoma in combination with chemotherapy and local heat treatment. 41,42 In our study, we compared the in vitro and in vivo delivery efficacy of liposome-mediated and adenovirusmediated GFP expression in HepG2 cancer cells (data unpublished).…”

Section: Discussionmentioning

confidence: 99%

A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells

Zhang¹,

Wang²,

Li³

et al. 2008

Cancer Biology & Therapy

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Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.

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Recent developments in the use of adenoviruses and immunotoxins in cancer gene therapy

Cited by 130 publications

References 139 publications

Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells

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