CD46 Represents a Target for Adenoviral Gene Therapy of Malignant Glioma

Ulasov, Ilya V.; Tyler, Matthew A.; Zheng, Sophy C.; Han, Yu; Lesniak, Maciej S.

doi:10.1089/hum.2006.17.ft-205

Cited by 20 publications

(29 citation statements)

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“…Ad.5/3 uses group B receptors, CD46 and CD80/CD86, and displays enhanced transduction of malignant glioma cells having low CAR (U87MG and U373MG) compared with wild-type Ad.5. 38,39 CD46 has also been shown to be overexpressed in some human neoplasms, 40 thereby protecting tumor cells from identification and destruction by the complement system, indicating a tumor-selective transduction ability by Ad.5/3. This concept was supported by the observation that Ad.5/3-Luc showed superior tumor-specific luciferase transgene expression when compared with Ad.5-Luc in normal human astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

Dash

Dmitriev

et al. 2010

Cancer Gene Ther

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Section: Discussionmentioning

confidence: 99%

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

Dash

Dmitriev

et al. 2010

Cancer Gene Ther

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“…This is a chimeric vector which contains the Ad5 backbone and Ad3 knob and binds to CD46 which is expressed on malignant brain tumors. 16 To investigate whether human survivin or …”

Section: © 2 0 0 7 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

“…Moreover, it provides a compelling argument for further preclinical development of CRAd-survivin-5/3, a novel oncolytic virus that utilizes the survivin promoter and contains a chimeric fiber protein encompassing adenovirus serotype 3 knob, which binds to CD46 expressed on malignant glioma. 16 …”

Section: Introductionmentioning

confidence: 99%

Comparative evaluation of survivin, midkine, and CXCR4 promoters for transcriptional targeting of glioma gene therapy

Ulasov¹,

Rivera²,

Sonabend³

et al. 2007

Cancer Biology & Therapy

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Objective: Transcriptional targeting is a key strategy to enhance therapeutic efficacy of gene therapy applications. In the context of oncolytic virotherapy, transcriptional promoter elements are used from genes that are over expressed in a variety of malignant cancers. In the present study, we examined the feasibility of transcriptional targeting to glioma cells by comparing the activity of survivin, midkine, and CXCR4 tumor-specific promoters.Methods: To evaluate the expression level of several glioma related genes, we performed quantitative RT-PCR analyses on samples obtained from cell lines and patients. To determine specific level of gene expression mediated by selective promoter elements, we measured luciferase expression in glioma samples transduced with replication deficient adenoviral vectors. Finally, we incorporated the optimal promoters into a conditionally replicative adenoviral vector, CRAd-5/3, and examined the cytopathic effect in vitro.Results: The survivin promoter demonstrated the highest level of mRNA expression in primary tumor samples and cell lines. Transcriptional targeting was confirmed by infection of glioma cells with an adenovirus expression vector containing a survivin-driven luciferase reporter gene. Of the tested promoters, minimal level of survivin activity was detected in normal human liver and brain. A novel vector, CRAd-survivin5/3, with E1a under the control of the survivin promoter, exhibited enhanced cytopathic effect in vitro.Conclusions: Our data demonstrate that the survivin promoter element is very active in glioma samples and has low activity in normal human brain and liver. A novel oncolytic virus, CRAd-survivin-5/3, was effective against a panel of glioma cell lines in vitro. Our results suggest that employing the survivin promoter element in the context of CRAd-5/3 may present a new opportunity for the development of glioma specific oncolytic vectors.

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“…MV entry to target cells is mediated by two membrane glycoproteins, the hemagglutin (H) protein and the fusion (F) protein. The H protein is responsible for binding to cellular receptors such as CD46, a regulator of complement activation that is found on all human nucleated cells and frequently overexpressed in tumor cells [3,4], including gliomas [5] and signaling lymphocyte activated molecule (SLAM) which is expressed on T-and B-lymphocytes and macrophages [6]. The F protein causes the virus to fuse with the cell after attachment has taken place.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic measles virus strains in the treatment of gliomas

Allen

Paraskevakou

Liu

et al. 2008

Expert Opinion on Biological Therapy

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Background-Recurrent gliomas have a dismal outcome despite use of multimodality treatment including surgery, radiation therapy and chemotherapy.Objective-In this article the authors discuss potential applications of oncolytic measles virus strains as novel antitumor agents in the treatment of gliomas.Methods-Important aspects of measles virus development as an anticancer therapeutic agent including engineering, retargeting and combination studies with other therapeutic modalities are discussed. The translational process that led to the first clinical trial of an engineered measles virus derivative in patients with recurrent glioblastoma multiforme is also described.Results/conclusions-Oncolytic measles virus strains hold promise as novel antitumor agents in the treatment of gliomas.

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CD46 Represents a Target for Adenoviral Gene Therapy of Malignant Glioma

Cited by 20 publications

References 1 publication

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

Comparative evaluation of survivin, midkine, and CXCR4 promoters for transcriptional targeting of glioma gene therapy

Oncolytic measles virus strains in the treatment of gliomas

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