The Experts below are selected from a list of 87 Experts worldwide ranked by ideXlab platform
Simon C. W. Richardson - One of the best experts on this subject based on the ideXlab platform.
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The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.
Expert opinion on drug delivery, 2016Co-Authors: Susan A. Shorter, Alexander S. Gollings, Monique A. M. Gorringe-pattrick, J. Emma Coakley, Paul D.r. Dyer, Simon C. W. RichardsonAbstract:ABSTRACTIntroduction: The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for ‘drug’ delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the ‘PEG dilemma’, balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem.Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking.Expert opinion: The possibility ...
Lingyun Sun - One of the best experts on this subject based on the ideXlab platform.
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p53 gene Gendicine and embolisation overcame recurrent hepatocellular carcinoma
Gut, 2005Co-Authors: Yongsong Guan, Yinkun Liu, X P Zhou, Lingyun SunAbstract:Transcatheter arterial chemoembolisation (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). However, this method is often unsuccessful. The p53 gene, which is present as a mutant form in many human tumours, is known to have broad spectrum antitumour effects when expressed normally. In this study, we report a 23 year old patient with recurrent HCC who was treated with the p53 gene (Gendicine) combining TACE, which resulted in a good clinical prognosis.
Zhaohui Peng - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Adenoviral-p53 Agent (Gendicine®): Quality Control, Mechanism of Action, and Its Use for Treatment of Malignant Tumors
Recent Advances in Cancer Research and Therapy, 2012Co-Authors: Shu-yuan Zhang, Zhaohui PengAbstract:This chapter introduces the current status of gene therapy and presents the antitumor mechanism of action, clinical trials and practice, manufacture process, quality control, gene therapy guideline, and intellectual property rights of the world’s first gene therapy drug recombinant human adenovirus-p53 injection trademarked as Gendicine approval in 2003.
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current status of Gendicine in china recombinant human ad p53 agent for treatment of cancers
Human Gene Therapy, 2005Co-Authors: Zhaohui PengAbstract:OVER THE PAST DECADE, gene therapy has been increasingly applied in clinical trials. According to data published by the Journal of Gene Medicine (http://www.wiley.co.uk/genetherapy/ clinical/), there were a total of 1020 approved gene therapy clinical trials in the world at the end of January 2005. Among these clinical trials, 66% were for the treatment of cancer. Of these cancer gene therapy trials, 58 used recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53). More than 20 kinds of cancer indications have been treated with rAd-p53 agent, such as head and neck squamous cell carcinoma (HNSCC), lung cancer, breast cancer, liver cancers. Various clinical treatment regimens have been evaluated, including administration of rAd-p53 agent alone or in combination with conventional therapies such as radiotherapy, chemotherapy, and surgery. Encouraging clinical responses have been reported by a number of study groups. Lang et al. (2003) reported the results of a phase I clinical trial study in which rAd-p53 was administered to 15 patients with recurrent glioma. rAd-p53 was injected intratumorally at doses between 3 1010 and 3 1012 viral particles (VP). Three days after rAd-p53 injection the tumor was resected and more rAd-p53 was injected into the tumor bed. Of the 15 patients treated, 1 survived more than 3 years without evidence of recurrence, 4 patients experienced no recurrence for more than 6 months after treatment, and 2 of these 4 patients survived for more than 1 year. In a multicenter phase II trial study involving 25 patients with non-small cell lung cancer, 7.5 1012 VP of rAd-p53 was injected intratumorally in combination with cisplatin and vinorelbine. No significant difference in tumor response was observed from rAd-p53-injected lesions and noninjected lesions (52 versus 48%, respectively); however, the rAd-p53-treated lesions appeared to be smaller than the nontreated controls (Schuler et al., 2001). In a separate clinical study of 24 patients with non-small cell lung cancer (Nemunaitis et al., 2000), rAd-p53 was injected intratumorally at doses between 1 106 and 1 1011 plaque-forming units (PFU)/injection in combination with cisplatin. Seventeen patients achieved stable disease, 2 patients achieved partial response, and 4 patients had progressive disease. Intratumoral injection of rAd-p53 in combination with cisplatin was well tolerated and there was evidence of clinical efficacy. rAd-p53 was also used for non-small cell lung cancer treatment in combination with radiation therapy (Swisher et al., 2003). The rAd-p53 dose ranged from 3 1011 to 3 1012 VP/injection. Radiation was given concurrently over 6 weeks to a total of 60 Gy. Of the 19 patients treated, 1 showed complete regression (5%), 11 demonstrated partial regression (58%), 3 showed stable disease (16%), 2 showed progressive disease (11%), and 2 were unevaluable (11%). In a bladder carcinoma trial, 12 patients received either intratumoral or intravesicular injections of rAdp53 at doses of 7.5 1011 to 7.5 1013 VP (Kuball et al., 2002). Higher transduction efficiency was observed when using the intravesicular delivery method. Seven of the 11 evaluable patients had evidence of p53 expression by reverse transcription-polymerase chain reaction (RT-PCR). Nine of the 12 patients were alive at a median follow-up of 30 months. Pagliaro et al. (2003) reported a similar phase I study in which rAd-p53 was instilled intravesicularly at 1 1012 VP/dose in 13 patients with locally advanced transitional cell carcinoma of the bladder. A preliminary antitumor effect was observed at a treatment dose of 1 1012 VP on days 1 and 4. Clayman et al. (1998) reported the results of a clinical study in which rAd-p53 was applied as a single agent to treat advanced recurrent head and neck squamous cell carcinoma. Thirty-three patients received an intratumoral injection of rAd-p53 at doses up to 1 1011 PFU/injection. Of the 17 evaluable patients, 2 patients showed objective tumor regression of greater than 50%, 6 patients presented stable disease for up to 3.5 months, and 9 patients showed progressive disease. In all the reported clinical studies, the most common side effects were pain at the injection site, fatigue, and development of self-limited fever. Overall, rAd-p53 treatment was well tolerated by patients, without serious side effects. On the basis of
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the genesis of Gendicine the story behind the first gene therapy
Biopharm International, 2004Co-Authors: Zhaohui PengAbstract:In this exclusive interview with BioPharm International, Dr. Zhaohui Peng - CEO and founder of Shenzhen SiBiono GeneTech - discusses the development, clinical trial results, and manufacture of Gendicine, the first gene therapy drug to gain regulatory approval.
G Zhu - One of the best experts on this subject based on the ideXlab platform.
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726 clinical trial of recombinant adenovirus p53 Gendicine combined with radiotherapy in nasopharyngeal carcinoma patients
Molecular Therapy, 2006Co-Authors: Shanwen Zhang, Shaowen Xiao, Yan Sun, Changqing Liu, G ZhuAbstract:The study was to evaluate the safety and the efficacy of recombinant adenovirus-p53 (Adp53, trademarked as Gendicine) combined with radiotherapy in nasopharyngeal carcinoma (NPC) patients. A controlled clinical trial on Gendicine combined with radiotherapy, that is, gene therapy + radiotherapy (GTRT), was conducted in 24 patients, and 25 patients treated with radiotherapy alone (RT) formed the control group. In the GTRT group, Gendicine 1|[times]|1012 virus particle (vp) was intratumorally injected once a week over to eight weeks, and concurrent irradiation was given. For both groups, the conventional fractionation 2Gy/day, five fractions a week, with a total dose of 70Gy in 35 fractions were given to either primary tumor or neck lymph node. Patients were monitored for adverse event and serum anti-adenoviral antibody, and tumors were monitored for response. A comparative study was performed between both groups on the immediate response rate by CT at the end of 4th week, 7th week and 2 months after the treatment. The median follow-up interval of surviving patients was 34.5 months (24|[sim]|45 months). Wild-type p53 gene therapy enhanced significantly radiotherapy efficacy by 1.59 times in patients with NPC at 4- week time point. Two months after the treatment complete response rate of GTRT group was 2.1 times that of RT group (62.5% v.s. 29.6%). The 3-year overall survival rate of GTRT group was 14.4% higher than that of GT group. No dose-limiting toxicity and adverse events were noted, except for transient fever after Gendicine administration. Intratumoral injection with Gendicine was safe and effective for patients with NPC.
Susan A. Shorter - One of the best experts on this subject based on the ideXlab platform.
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The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.
Expert opinion on drug delivery, 2016Co-Authors: Susan A. Shorter, Alexander S. Gollings, Monique A. M. Gorringe-pattrick, J. Emma Coakley, Paul D.r. Dyer, Simon C. W. RichardsonAbstract:ABSTRACTIntroduction: The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for ‘drug’ delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the ‘PEG dilemma’, balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem.Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking.Expert opinion: The possibility ...