Enhanced antitumor efficacy of a novel fiber chimeric oncolytic adenovirus expressing p53 on hepatocellular carcinoma

Chen, Wei; Wu, Yuqiang; Liu, Wei; Wang, Guoying; Wang, Xiaoyun; Yang, Yang; Chen, Wenjie; Tai, Yan; Mao, Lu; Qian, Qijun; Zhang, Qi; Chen, Guihua

doi:10.1016/j.canlet.2011.03.021

Cited by 28 publications

(18 citation statements)

References 32 publications

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“…Importantly, p63 and p73 isoforms were not sufficient to compromise Adp53sensor replication, demonstrating that this approach was not restricted by other p53 family members in HCC cells [111]. Thus, novel virotherapeutic strategies based on p53 integrity may overcome limitations of previous oncolytic approaches and some studies suggested that HCC cells are promising targets [112,113].…”

Section: Gene Therapeutic Approachesmentioning

confidence: 94%

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Malz

Pinna

Schirmacher

et al. 2012

Journal of Hepatology

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Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies with poor prognosis and increasing incidence in the Western world. Only for a minority of HCC patients, surgical treatment options offer potential cure and therapeutic success of pharmacological approaches is limited. Highly specific approaches (e.g., kinase inhibitors) did not significantly improve the situation so far, possibly due to functional compensation, genetic heterogeneity of HCC, and development of resistance under selective pressure. In contrast, transcriptional regulators (especially transcription factors and co-factors) may integrate and process input signals of different (oncogenic) pathways and therefore represent cellular bottlenecks that regulate tumor cell biology. In this review, we want to summarize the current knowledge about central transcriptional regulators in human hepatocarcinogenesis and their potential as therapeutic target structures. Genomic and transcriptomic data of primary human HCC revealed that many of these factors showed up in subgroups of HCCs with a more aggressive phenotype, suggesting that aberrant activity of transcriptional regulators collect input information to promote tumor initiation and progression. Therefore, expression and dysfunction of transcription factors and co-factors may gain relevance for diagnostics and therapy of HCC.

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Section: Gene Therapeutic Approachesmentioning

confidence: 94%

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Malz

Pinna

Schirmacher

et al. 2012

Journal of Hepatology

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“…Surgical resection, transplantation, and ablation are highly-effective treatments, with curative potential, for early-stage HCC (Bruix and Sherman, 2011). Unfortunately, over 80% of HCC cases are usually diagnosed at an advanced stage, where systemic dissemination and metastases have already occurred, and, consequently, these surgical procedures are no longer a viable treatment option (Chen et al, 2011;Llovet, 2005). Since metastasis is the most frequent cause of death, it is necessary to develop effective systemic therapy to prevent disease progression and improve survival for patients with advanced HCC (Thomas, 2008).…”

Section: Introductionmentioning

confidence: 99%

Long-term toxicity study of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys by intravenous injection

Yue

Shen

et al. 2015

Regulatory Toxicology and Pharmacology

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“…CD46 also acts as a receptor for numerous pathogenic microbes, including group B adenoviruses [18]. CD46 is also overexpressed in some human cancers, including lymphomas, breast cancers, ovarian cancers, hepatocellular carcinomas [19–22], thus protecting cancer cells from the complement system. Therefore, group B Ads are attractive gene therapy vectors since they can overcome the limitations in tumor transduction efficacy through utilizing more ubiquitously expressed CD46.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers

Cho

Kwon

et al. 2016

Oncotarget

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CD46 is a complement inhibitor membrane cofactor which also acts as a receptor for various microbes, including species B adenoviruses (Ads). While most Ad gene therapy vectors are derived from species C and infect cells through coxsackie-adenovirus receptor (CAR), CAR expression is downregulated in many cancer cells, resulting inefficient Ad-based therapeutics. Despite a limited knowledge on the expression status of many cancer cells, an increasing number of cancer gene therapy studies include fiber-modified Ad vectors redirected to the more ubiquitously expressed CD46. Since our finding from tumor microarray indicate that CD46 was overexpressed in cancers of the prostate and colon, fiber chimeric Ad5/35 vectors that have infection tropism for CD46 were employed to demonstrate its efficacy in colorectal cancers (CRC). CD46-overexpressed cells showed a significantly higher response to Ad5/35-GFP and to Ad5/35-tk/GCV. While CRC cells express variable levels of CD46, CD46 expression was positively correlated with Ad5/35-mediated GFP fluorescence and accordingly its cell killing. Injection of Ad5/35-tk/GCV caused much greater tumor-suppression in mice bearing CD46-overexpressed cancer xenograft compared to mock group. Analysis of CRC samples revealed that patients with positive CD46 expression had a higher survival rate (p=0.031), carried tumors that were well-differentiated, but less invasive and metastatic, and with a low T stage (all p<0.05). Taken together, our study demonstrated that species B-based adenoviral gene therapy is a suitable approach for generally CD46-overexpressed CRC but would require careful consideration preceding CD46 analysis and categorizing CRC patients.

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Enhanced antitumor efficacy of a novel fiber chimeric oncolytic adenovirus expressing p53 on hepatocellular carcinoma

Cited by 28 publications

References 32 publications

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Long-term toxicity study of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys by intravenous injection

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers

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