Gendicine is a

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

medication used to treat patients with

head and neck squamous cell carcinoma Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat (nasopharyngeal, oropharyn ...

linked to

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in the ''TP53'' gene. It consists of recombinant

adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from t ...

engineered to code for p53 protein (rAd-p53) and is manufactured by Shenzhen SiBiono GeneTech. Gendicine was the first gene therapy product to obtain regulatory approval for clinical use in humans after Chinese

State Food and Drug Administration The National Medical Products Administration (NMPA; ) is a national bureau responsible for drug supervision under the State Council of China and is managed by the State Administration for Market Regulation. History The agency had multiple fo ...

approved it in 2003. As of 2024, Gendicine has not been approved for use in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

and the

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

. __TOC__

Mechanism of action

Gendicine enters the tumour cells by way of

receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This ...

and begins to over-express genes coding for the p53 protein needed to fight the tumour. 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 Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...

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. Ad-p53 appears to act synergistically with conventional treatments such as chemo- and

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

. This synergy still exists in patients with chemotherapy and radiotherapy-resistant tumors. Gendicine produces fewer side effects than conventional therapy.

Related development

Contusugene ladenovec (Advexin), a similar gene therapy developed by

Introgene Janssen Vaccines, formerly Crucell, is a biotechnology company specializing in vaccines and biopharmaceutical technologies. It was formed when Johnson & Johnson acquired the Dutch biotech company Crucell. Janssen Vaccines is part of Johnson & Jo ...

that also uses adenovirus to deliver the p53 gene, was turned down by the FDA in 2008 and withdrawn by the maker from the EMA approval shortly after.

References

{{Reflist Gene delivery Adenoviridae Immunotherapy Gene therapy