"
Team:SupBiotech-Paris/Conclusion3
From 2009.igem.org
Introduction Current therapies Gene therapies DVS Concept Tissue Vector Cell Vector Therapeutic plasmid Conclusion Implementation Tissue targeting Antitumor action Treatment modeling Conclusion
BioBricks Material & Method Bibliography
Conclusion
Non-small cell lung cancer, or NSCLC, is an aggressive cancer. It grows in the lumen of the organ at high speed. This localization is highly correlated to the localization of factors launching the tumorgenesis (contained in the tobacco smoke for example). Tumor cells lose their apoptotic capacity after the functional loss of different tumor suppressors playing a role in the apoptotic pathway. The DVS application in the fight against cancer is based on the fact to reactivate these apoptotic pathway by bringing into tumor cells a wild-type version of genes coding for an healthy version of a non-functional tumor suppressor gene. The [http://www.sanger.ac.uk/genetics/CGP/cosmic/ COSMIC project] of [http://www.sanger.ac.uk/ Sanger institute] allows us to inventory genes the most likely to be mutated in the case of lung cancer. So, we had to determine the therapeutic plasmid composition applied to this physiopathology.
Several studies showed that lung is one of the Mycobactérium avium natural tropism in mouse and Human. After an intravenous injection of M. avium, the tissue vector gets to the lung and can grow inside it. So, the first DVS concept, for these application, is validated. For the second one, literature shows that the creation of a recombined phage with an adenovirus penton base, a protein which allows to pass through membranes by endocytosis, is possible. The cell vector creation, which has for objective to integer the therapeutic plasmid into eukaryotic tumor cells, is feasible. It is proved that we can modulate the efficiency of the interaction of the penton base with integrins of eukaryotic cells by using the whole protein or only its RGD sequence alone. In the DVS project context it is the entire structure of the protein that we placed on the Lambda phage capsid. Possessing a lower affinity for cell than if we used the RGD motif alone, cell vectors could more scatter and consequently, touch a higher number of cells.
In vivo studies on human proved that to bring a wild-type version of a tumor suppressor gene into tumor cell for which the gene is mutated allow the launching of the apoptosis process and the inhibition of the tumor growth.
By taking up all these data, it appears obvious that the DVS application in the anticancer fight against non small cell lung cancer represent a straight alternative to existing treatments, the tissue vector targeting the organ of interest and the cell vector could deliver the therapeutic plasmid which apoptotic activity is confirmed.
