Conditionally replicative adenovirus expressing degradation-resistant p53 for enhanced oncolysis of human cancer cells overexpressing murine double minute 2

Beusechem, Victor W. van; Doel, Petra B. van den; Gerritsen, Winald R.

doi:10.1158/1535-7163.mct-05-0010

Cited by 23 publications

(25 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Strategies for temporarily blocking the function of reticuloendothelial cells and hepatic uptake during intravascular administration of vectors have been reported already by the laboratories of Seymour [51][52] and Gerritsen, 53 respectively. These include: bisphosphonates and Gadolinium to inhibit the function of the reticulendothelial cells, reactive polymers to cover the charges of the adenoviral vector, [51][52] and mutational change of the adenoviral vector fiber protein and the penton base proteins, to decrease uptake into the hepatocytes.…”

Section: Adenoviral Vectorsmentioning

confidence: 99%

See 1 more Smart Citation

Tumor vascular targeting therapy with viral vectors

Liu

Deisseroth

2006

Blood

View full text Add to dashboard Cite

Section: Adenoviral Vectorsmentioning

confidence: 99%

“…These include: bisphosphonates and Gadolinium to inhibit the function of the reticulendothelial cells, reactive polymers to cover the charges of the adenoviral vector, [51][52] and mutational change of the adenoviral vector fiber protein and the penton base proteins, to decrease uptake into the hepatocytes. 53 …”

Section: Adenoviral Vectorsmentioning

confidence: 99%

Tumor vascular targeting therapy with viral vectors

Liu

Deisseroth

2006

Blood

View full text Add to dashboard Cite

“…Importantly, we found previously that exogenous p53 expression enhanced the cancer cell killing potency of an oncolytic adenovirus (17). Recently, however, we found that high expression of MDM2 limited the anticancer effect of exogenous p53 expressed by oncolytic adenoviruses (18).…”

Section: Introductionmentioning

confidence: 83%

Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53

Graat

Carette

Schagen

et al. 2007

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

Strategies to treat cancer by restoring p53 tumor suppressor functions are being actively investigated. These approaches range from expressing an exogenous p53 gene in p53 mutant cancers to antagonizing a p53 inhibitor in p53 wild-type (WT) cancer cells. In addition, exogenous p53 is used to strengthen the anticancer efficacy of oncolytic adenoviruses. Many cancers express high levels of the major negative regulator of p53, mouse double minute 2 (MDM2) protein. Recently, a novel class of highly potent and specific MDM2 antagonists, the Nutlins, was identified. We envisioned that Nutlins could protect both endogenous and exogenous p53 from MDM2-mediated inactivation. We therefore investigated treating human cancer cells with a combination of adenovirus-mediated p53 gene therapy and Nutlin. Combination treatment resulted in broadly effective cell kill of p53 WT and p53-negative cancer cells. Cytotoxicity was associated with profound cell cycle checkpoint activation and apoptosis induction. We also tested Nutlin in combination with oncolytic adenoviruses. Nutlin treatment accelerated viral progeny burst from oncolytic adenovirus-infected cancer cells and caused an estimated 10-to 1,000-fold augmented eradication of p53 WT cancer cells. These findings suggest that Nutlins are promising compounds to be combined with p53 gene therapy and oncolytic virotherapy for cancer.

show abstract

“…Paradoxically, enhanced p53 expression increased the oncolytic potency of CRAds in the presence of E1B-55kD (30,31). The dilemma can be explained by two phenomena.…”

Section: Discussionmentioning

confidence: 99%

A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells

Liu

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

E1B-55kD-deleted adenoviruses have been used as conditionally replicative adenoviruses (CRAds) for therapeutic purposes in tumors with loss-of-function p53 mutation. To target cancer cells that harbor activating mutant KRAS (KRAS aMut ) but spare p53 wild normal cells, we constructed and examined by reporter assays a KRAS aMut but not p53-responsive promoter, the Δp53REP2 promoter. The Δp53REP2 promoter, derived from human double minute 2 (hdm2) P2 promoter with its p53 response elements being deleted, was used to regulate the expression of the hdm2 transgene in a novel E1B-55kD-deleted CRAd, the

show abstract

Conditionally replicative adenovirus expressing degradation-resistant p53 for enhanced oncolysis of human cancer cells overexpressing murine double minute 2

Cited by 23 publications

References 28 publications

Tumor vascular targeting therapy with viral vectors

Tumor vascular targeting therapy with viral vectors

Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53

A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells

Contact Info

Product

Resources

About