Adenoviruses with an alpha v beta integrin targeting moiety in the fiber shaft or the HI-loop increase tumor specificity without compromising antitumor efficacy in magnetic resonance imaging of colorectal cancer metastases

Colorectal cancer is often a deadly disease and cannot be cured at metastatic stage. Oncolytic adenoviruses have been considered as a new therapeutic option for treatment of refractory disseminated cancers, including colorectal cancer.

The safety data has been excellent but tumor transduction and antitumor efficacy especially in systemic administration needs to be improved.

Methods: Here, the utility of alpha v beta integrin targeting moiety Arg-Gly-Asp (RGD) in the Lys-Lys-Thr-Lys (KKTK) domain of the fiber shaft or in the HI-loop of adenovirus serotype 5 for increased tumor targeting and antitumor efficacy was evaluated. To this end, novel spleen-to-liver metastatic colorectal cancer mouse model was used and the antitumor efficacy was evaluated with magnetic resonance imaging (MRI).

Results: Both modifications (RGD in the HI-loop or in the fiber shaft) increased gene transfer efficacy in colorectal cancer cell lines and improved tumor-to-normal ratio in systemic administration of the vector.

Conclusions: Antitumor potency was not compromised with RGD modified viruses suggesting increased safety profile and tumor specificity.

Author: Sergio Lavilla-AlonsoGerd BauerschmitzUsama Abo-RamadanJuha HalavaaraSophie EscutenaireIulia DiaconuTurgut TatlisumakAnna KanervaAkseli HemminkiSari Pesonen
Credits/Source: Journal of Translational Medicine 2010, 8:80

Published on: 2010-08-23

Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.

Comments Page 0 of 0

There are currently 0 comments to display.

+ Add New Comment

Custom Search