Phase I/II adenoviral <i>p53</i> gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma

Shimada, Hideaki; Matsubara, Hisahiro; Shiratori, Tooru; Shimizu, Takanori; Miyazaki, Shinichi; Okazumi, Shinichi; Nabeya, Yoshihiro; Shuto, Kiyohiko; Hayashi, Hideki; Tanizawa, Tooru; Nakatani, Yukio; Nakasa, Hiromitsu; Kitada, Mitsukazu; Ochiai, Takenori

doi:10.1111/j.1349-7006.2006.00206.x

Cited by 73 publications

(53 citation statements)

References 17 publications

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“…Therapies targeting TP53 loss of function are currently being examined in clinical trials, and several studies suggest that patients harboring TP53 alterations will respond better to angiogenesis inhibitors [45] . The efficacy of intra-tumor injection of p53 adenovirus (Advexin, Introgen Therapeutics Inc., Austin, TX, United States) has been confirmed in Japanese ESCC patients [46] . Additionally, a TP53 adenoviral-based treatment (Gendicine, Shenshen Sibiono Genetech, Shenzhen, China) for patients with squamous cell carcinoma of the head and neck has recently been approved for use in China [47] .…”

Section: P53 Familymentioning

confidence: 99%

Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

Sasaki¹,

Tamura²,

Koyama³

et al. 2016

WJG

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Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53 , CDKN2A , FAT1 , NOTCH1 , PIK3CA , KMT2D and NFE2L2 , which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC.

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Section: P53 Familymentioning

confidence: 99%

Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

Sasaki¹,

Tamura²,

Koyama³

et al. 2016

WJG

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“…Our clinical study with Ad-p53 for esophageal carcinoma, however, could not support the assumption because of its limited patient numbers. 4 Esophageal carcinoma cells with the wild-type p53 tend to express CAR better than those with mutated p53, which has not been evidenced by other types of tumors, and this putative relationship needs further studies with more esophageal specimens. We also believe that clinical studies conducted for other cancer types using Ad-p53 require re-evaluation of the efficacy from the standpoint of CAR expression levels.…”

Section: Discussionmentioning

confidence: 94%

“…We reported that Ad-p53 produced cytotoxic effects for esophageal carcinoma cells and have recently completed a phase I/II clinical trial for cancer patients with Ad-p53. 3,4 The clinical study showed that intratumoral injection of Ad-p53 was safe and produced antitumor effects with variable efficacy. 4 Multiple mechanisms of the Ad-p53-mediated antitumor activities are well demonstrated and apoptosis induction is one of the direct actions of tumors.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 The clinical study showed that intratumoral injection of Ad-p53 was safe and produced antitumor effects with variable efficacy. 4 Multiple mechanisms of the Ad-p53-mediated antitumor activities are well demonstrated and apoptosis induction is one of the direct actions of tumors. 5 Ad defective of E1B55 kDa molecules (Ad-delE1B55) have been also investigated for clinical feasibility in various cancer types including head and neck cancer.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status

Kawamura

et al. 2009

Cancer Gene Ther

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We examined cytotoxic effects of adenoviruses (Ad) expressing the p53 gene (Ad-p53) in nine human esophageal carcinoma cell lines with respect to the Ad receptor expression and the endogenous p53 gene status. Ad-p53-mediated cytotoxicity was related with an expression level of the coxsackievirus adenovirus receptor (CAR) but not with that of CD51, both of which are type 5 Ad receptors. Contrary to earlier studies, we found that the cytotoxicity was greater in tumor cells with the wild-type p53 gene than in those with mutated p53. The cytotoxic activity of Ad defective of E1B55kDa molecules (Ad-delE1B55), however, was not linked with the CAR expression level or the endogenous p53 status. We noticed that the tumor cells with the wild-type p53 gene showed greater CAR expression levels, although transduction with Ad-p53 did not upregulate the CAR expression in the mutated cells. We also examined the Ad-53-mediated cytotoxicity in two kinds of paired fibroblasts, parent and immortalized with loss of the p53 functions, and showed that the CAR expression level was more influential than the endogenous p53 status in the cytotoxicity. These data suggest that CAR expression level is a better predictive marker than endogenous p53 status for Ad-p53-mediated cytotoxicity in esophageal carcinoma.

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“…[24][25][26] When used as vaccine vectors, on the other hand, Ad vectors are intramuscularly injected. 27,28 In addition, Ad vectors are intramyocardially injected in angiogenic gene therapy.…”

Section: Spleen and Nasal Cavitymentioning

confidence: 99%

Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates

Sakurai

Akitomo

et al. 2008

Gene Ther

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Adenovirus (Ad) serotype 35 (Ad35) vectors have attracted remarkable attention as alternatives to conventional Ad serotype 5 (Ad5) vectors. In a previous study, we showed that intravenously administered Ad35 vectors exhibited a safer profile than Ad5 vectors in cynomolgus monkeys, which ubiquitously express CD46, an Ad35 receptor, in a pattern similar to that in humans. However, the Ad35 vectors poorly transduced the organs. In this study, we examined the transduction properties of Ad35 vectors after local administration into organs of cynomolgus monkeys. The vectors transduced different types of cells depending on the organ. Hepatocytes and microglia were mainly transduced after the vectors were injected into the liver and cerebrum, respectively. Injection of the vectors into the femoral muscle resulted in the transduction of cells that appeared to be fibroblasts and/or macrophages. Conjunctival epithelial cells showed transgene expression following infusion into the vitreous body of the eyeball. Transgene expression was limited to areas around the injection points in most of the organs. In contrast, Ad35 vector-mediated transgene expression was not detected in any of the organs not injected with Ad35 vectors. These results suggest that Ad35 vectors are suitable for gene delivery by direct administration to organs.

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Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma

Cited by 73 publications

References 17 publications

Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status

Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates

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