Preview
Sign-in for full Details 
Sign-in free and Explore the Exciting World of BiomedExperts:
- Over 1.500.000 Profiles
- More than 1.800 Organizations worldwide
- State of the Art Network Visualizations
- Manage your own Profile
- Locate Experts in your Country/Region
- Locate Experts in your 1. and 2. Level Network
- Connect to Experts Worldwide
find experts for
Sign-in to see more
2002:
Haviv Yosef S; Blackwell Jerry L; Kanerva Anna; Nagi Peter; Krasnykh Victor; Dmitriev Igor; Wang Minghui; Naito Seiji; Lei Xiaosheng; Hemminki Akseli; Carey Delicia; Curiel David T
Adenoviral gene therapy for renal cancer requires retargeting to alternative cellular receptors.
Cancer research 2002;
62(
15):.
Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies in humans. Therefore, the identification of new agents with better antitumor activity merits a high priority in the treatment of advanced RCC. In this regard, gene therapy with adenoviral (Ad) vectors is a promising new modality for cancer. However, a primary limiting factor for the use of Ad vectors for cancer gene therapy is their critical dependence on cellular expression of the primary Ad receptor, the coxsackie and adenovirus receptor (CAR), known to be down-regulated in many cancer types. Following the identification of CAR deficiency in RCC lines, we have found abundant membrane expression of alpha(v)beta 3 and alpha(v)beta 5 integrins and of the putative receptor to Ad serotype 3 (Ad3). As an alternative gene therapy approach for RCC that would circumvent CAR deficiency, we employed retargeting of replication-incompetent Ad vectors and replication-competent Ad viruses to alpha(v)beta 3 and alpha(v)beta 5 integrins and to the putative Ad3 receptor. These strategies to genetically alter Ad tropism were based on either the insertion of a cysteine-aspartate-cysteine-arginine-glycine-aspartate-cysteine-phenylalanine-cysteine (RGD) motif into the HI loop of the Ad fiber knob domain or on generation of a chimeric Ad fiber composed of adenovirus serotype 5 shaft/Ad3 knob. Both strategies proved highly efficient to circumvent CAR deficiency and enhance gene delivery into RCC cells. Furthermore, in the context of replication-competent Ad, tropism alteration resulted in distinct capacity of the retargeted viruses to infect, replicate, and lyse RCC models in vitro and in vivo. The retargeting strategies were particularly beneficial in the context of replication-competent Ad. These findings underscore the importance of CAR-independent cellular entry mechanisms in RCC and are highly consequential for the development of viral antitumor agents for RCC and other CAR-negative tumors.
Post to CiteULike 
Sign in free and see...
Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more
