Gendicine is a recombinant adenovirus engineered to express

wildtype The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, " ...

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

(rAd-p53). This virus is designed to treat patients with tumors which have mutated p53 genes. __TOC__

History

Gendicine is the first

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

product approved for clinical use in humans. 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. 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 based in Leiden and placed it in their ph ...

that also uses adenovirus to deliver the p53 gene, was turned down by the FDA in 2008 and withdrawn by the maker from the EMA approval shortly after.

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

References

Gene delivery Adenoviridae {{Genetics-stub Immunotherapy Gene therapy