Docetaxel plus trans-tracheal injection of adenoviral-mediated p53 versus docetaxel alone in patients with previously treated non-small-cell lung cancer

Xia, Ning; Sun, Zhenliang; Wang, Y; Zhou, Jiaxin; Chen, S; Chen, D; Zhang, H

doi:10.1038/cgt.2011.15

Cited by 11 publications

(9 citation statements)

References 17 publications

(15 reference statements)

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“…Although molecular-targeted cancer therapy has advanced considerably, chemotherapy is the primary treatment for lung cancer cases that are unresectable. For patients with advanced NSCLC, the platinum-based two-drug combination regimen is a standard chemotherapy (3,4). Cisplatin (CDDP)-based chemotherapy has improved the survival rate of patients with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Effect of the p53α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line

2017

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To investigate the effects of tumor protein p53 (p53 or TP53) α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line, the recombinant vector pEGFP-p53α was constructed. The vector pEGFP-p53α was transfected into the cultured p53-null H1299 cells using Lipofectamine 2000. The G418-resistant cells were then selected. The expression of the p53α gene in these cells was examined using reverse transcription-polymerase chain reaction, and TP53 protein expression was examined using western blot analysis and immunocytochemistry. An MTT assay and colony formation assay were used to analyze the response of the transfected cells to cisplatin (CDDP). DAPI staining was used to determine the level of apoptosis of the transfected cells. The transfected H1299 human lung adenocarcinoma cells stably expressed TP53 protein. The MTT assay demonstrated that the 50% inhibitory concentrations for the H1299, H1299/pEGFP-N1 and H1299/pEGFP-p53α cells were 28, 24 and 18 µmol/l, respectively. The survival rate of H1299/pEGFP-p53α cells was significantly reduced compared with that of H1299 and H1299/pEGFP-N1 cells (P<0.05). The colony formation assay and DAPI staining identified that the colony formation rate and the number of apoptotic cells of H1299/pEGFP-p53α were significantly reduced, compared with those of the H1299 and H1299/pEGFP-N1 cells (P<0.05). Therefor, the present study demonstrated that the transfection of H1299 cells with the p53α gene resulted in an increase in sensitivity to CDDP chemotherapy. The combination of CDDP and gene therapy for H1299 lung adenocarcinoma cell line provides an experimental basis for clinical research.

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Section: Introductionmentioning

confidence: 99%

Effect of the p53α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line

2017

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“…Although both methods showed improved results compared to the control group, the response rate for Gendicine combined with chemotherapy and radiotherapy was 76.9%, which was higher than that for Gendicine combined with chemotherapy alone (47.3%, 48.0%, and 10.5%). [66][67][68][69] All reports concluded there was improved efficacy and quality of life for the patients. [66][67][68][69]81 Breast cancer.…”

Section: Use Of Gendicine To Treat Head and Neck Cancermentioning

confidence: 99%

“…[66][67][68][69] All reports concluded there was improved efficacy and quality of life for the patients. [66][67][68][69]81 Breast cancer. A clinical study on use of Gendicine to treat triple-negative breast cancer has been conducted in China (manuscript in preparation).…”

Section: Use Of Gendicine To Treat Head and Neck Cancermentioning

confidence: 99%

The First Approved Gene Therapy Product for Cancer Ad-p53(Gendicine): 12 Years in the Clinic

et al. 2018

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Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004. Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions. Based on 12 years of commercial use in >30,000 patients, and >30 published clinical studies, Gendicine has exhibited an exemplary safety record, and when combined with chemotherapy and radiotherapy has demonstrated significantly higher response rates than for standard therapies alone. In addition to head and neck cancer, Gendicine has been successfully applied to treat various other cancer types and different stages of disease. Thirteen published studies that include long-term survival data showed that Gendicine combination regimens yield progression-free survival times that are significantly longer than standard therapies alone. Although the p53 gene is mutated in >50% of all human cancers, p53 mutation status did not significantly influence efficacy outcomes and long-term survival rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements, and 169,571 vials (1.0 × 10 vector particles per vial) have been used to treat patients. No serious adverse events have been reported, except for vector-associated transient fever, which occurred in 50-60% of patients and persisted for only a few hours. The manufacturing accomplishments and clinical experience with Gendicine, as well as the understanding of its cellular mechanisms of action and implications, could provide valuable insights for the international gene therapy community and add valuable data to promote further developments and advancements in the gene therapy field.

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“…Disappointingly, for patients with relapsed NSCLC, transtracheal injection of Adp53 in addition to docetaxel did not improve overall survival or efficacy. 43 …”

Section: Clinical Utility Of the Replication-deficient Adp53-based Gementioning

confidence: 99%

Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives

Chen

Zhang²,

et al. 2014

OTT

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Gene therapy has promised to be a highly effective antitumor treatment by introducing a tumor suppressor gene or the abrogation of an oncogene. Among the potential therapeutic transgenes, the tumor suppressor gene p53 serves as an attractive target. Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary deoxyribonucleic acid copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). Preclinical in vitro and in vivo studies have shown that Adp53 triggers a dramatic tumor regression response in various cancers. These viruses are engineered to lack certain early proteins and are thus replication defective, including Gendicine, SCH-58500, and Advexin. Several types of tumor-specific p53-expressing conditionally replicating adenovirus vectors (known as replication-competent CRAdp53 vectors) have been developed, such as ONYX 015, AdDelta24-p53, SG600-p53, OBP-702, and H101. Various clinical trials have been conducted to investigate the safety and efficiency of these adenoviral vectors. In this review we will talk about the biological mechanisms, clinical utility, and therapeutic potentials of the replication-deficient Adp53-based and replication-competent CRAdp53-based gene therapy.

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Docetaxel plus trans-tracheal injection of adenoviral-mediated p53 versus docetaxel alone in patients with previously treated non-small-cell lung cancer

Cited by 11 publications

References 17 publications

Effect of the p53α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line

Effect of the p53α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line

The First Approved Gene Therapy Product for Cancer Ad-p53(Gendicine): 12 Years in the Clinic

Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives

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