Gendicine

Gendicine is a recombinant adenovirus engineered to express wildtype-p53 (rAd-p53). This virus is designed to treat patients with tumors which have mutated p53 genes.

History

Gendicine is the first gene therapy product approved for clinical use in humans.[1] Gendicine is manufactured by Shenzhen SiBiono GeneTech. Gendicine was approved in 2003 by the Chinese State Food and Drug Administration to treat head and neck squamous cell carcinoma.[2]

Contusugene ladenovec (Advexin), a similar gene therapy developed by Introgene that also uses adenovirus to deliver the p53 gene, was turned down by the FDA in 2008[3] and withdrawn by the maker from the EMA approval shortly after.[4]

Mechanism of action

Gendicine enters the tumour cells by way of receptor-mediated endocytosis and begins to over-express genes coding for the p53 protein needed to fight the tumour.[5] Ad-p53 seems to act by stimulating the apoptotic pathway in tumour cells, which increases the expression of tumour suppressor genes and immune response factors (such as the ability of natural killer (NK) cells to exert "bystander" effects). It also decreases the expression of multi-drug resistance, vascular endothelial growth factor and matrix metalloproteinase-2 genes and blocking transcriptional survival signals.

p53 mutation status of the tumour cells and response to Ad-p53 treatment are not closely correlated.[6] Ad-p53 appears to act synergistically with conventional treatments such as chemo- and radiotherapy. This synergy still exists in patients with chemotherapy and radiotherapy-resistant tumors. Gendicine produces fewer side effects than conventional therapy.

References

Zhang, Wei-Wei; Li, Longjiang; Li, Dinggang; Liu, Jiliang; Li, Xiuqin; Li, Wei; Xu, Xiaolong; Zhang, Michael J.; Chandler, Lois A.; Lin, Hong; Hu, Aiguo (2018-02-01). "The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years in the Clinic". Human Gene Therapy. 29 (2): 160–179. doi:10.1089/hum.2017.218. ISSN 1043-0342. PMID 29338444.
Pearson S, Jia H, Kandachi K (2004). "China approves first gene therapy". Nature Biotechnology. 22 (1): 3–4. doi:10.1038/nbt0104-3. PMC 7097065. PMID 14704685.
Osborne R (2008). "Ark floats gene therapy's boat, for now". Nature Biotechnology. 26 (26): 1057–1059. doi:10.1038/nbt1008-1057. PMID 18846056. S2CID 74421879.
European Medicines Agency. "Advexin: Withdrawal of the marketing authorisation application". Retrieved 9 August 2020.
Peng, Zhaohui (May 1, 2004). "The Genesis of Gendicine: The Story Behind the First Gene Therapy". Biopharm International.
Zhaohui Peng (2005). "Current Status of Gendicine in China: Recombinant Human Ad-p53 Agent for Treatment of Cancers" (PDF). Human Gene Therapy (16): 1016–1027.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] Zhang, Wei-Wei; Li, Longjiang; Li, Dinggang; Liu, Jiliang; Li, Xiuqin; Li, Wei; Xu, Xiaolong; Zhang, Michael J.; Chandler, Lois A.; Lin, Hong; Hu, Aiguo (2018-02-01). "The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years in the Clinic". Human Gene Therapy. 29 (2): 160–179. doi:10.1089/hum.2017.218. ISSN 1043-0342. PMID 29338444.

[Gend-2] Pearson S, Jia H, Kandachi K (2004). "China approves first gene therapy". Nature Biotechnology. 22 (1): 3–4. doi:10.1038/nbt0104-3. PMC 7097065. PMID 14704685.

[3] Osborne R (2008). "Ark floats gene therapy's boat, for now". Nature Biotechnology. 26 (26): 1057–1059. doi:10.1038/nbt1008-1057. PMID 18846056. S2CID 74421879.

[4] European Medicines Agency. "Advexin: Withdrawal of the marketing authorisation application". Retrieved 9 August 2020.

[5] Peng, Zhaohui (May 1, 2004). "The Genesis of Gendicine: The Story Behind the First Gene Therapy". Biopharm International.

[6] Zhaohui Peng (2005). "Current Status of Gendicine in China: Recombinant Human Ad-p53 Agent for Treatment of Cancers" (PDF). Human Gene Therapy (16): 1016–1027.