Navigation Links
Adenoviral vector specifically targeted to EphA2 receptor in pancreatic cancer cells

Pancreatic cancer is a devastating disease with poor prognosis. This warrants the development of novel therapies including gene therapy. However, clinical studies have demonstrated poor efficacy of adenoviral gene therapy because of the absence of adenoviral binding sites on pancreatic cancer cells such as the coxsackie and adenovirus receptor (CAR). Circumventing CAR-mediated entry therefore seems a promising option to improve adenoviral entry into pancreatic cancer cells and to enhance the efficacy of adenoviral vectors.

A research team led by Dr. Piter J Bosma from University of Amsterdam addressed this question. Their study will be published on June 14, 2009 in the World Journal of Gastroenterology.

They present a novel adenoviral vector that binds to the EphA2 receptor (EphA2R). This receptor is highly expressed in several solid tumors including pancreatic cancer. YSA, a small peptide ligand that binds the EphA2R with high affinity, was inserted into the HI loop of the adenovirus serotype 5 fiber knob. To further increase the specificity of this vector, binding sites for native adenoviral receptors, the coxsackie and adenovirus receptor (CAR) and integrin, were ablated from the viral capsid. The ablated retargeted adenoviral vector was produced on 293T cells. Specific targeting of this novel adenoviral vector to pancreatic cancer was investigated on established human pancreatic cancer cell lines. Upon demonstrating specific in vitro targeting, in vivo targeting to subcutaneous growing human pancreatic cancer was tested by intravenous and intraperitoneal administration of the ablated adenoviral vector.

They found that ablation of native cellular binding sites reduced adenoviral transduction at least 100-fold. Insertion of the YSA peptide in the HI loop restored adenoviral transduction of EphA2R-expressing cells but not of cells lacking this receptor. YSA-mediated transduction was inhibited by addition of synthetic YSA peptide. The transduction specificity of the ablated retargeted vector towards human pancreatic cancer cells was enhanced almost 10-fold in vitro. In a subsequent in vivo study of a nude (nu/nu ) mouse model however, no increased adenoviral targeting to subcutaneously growing human pancreas cancer nodules was seen upon injection into the tail vein, nor upon injection into the peritoneum.

Although re-directing of the adenoviral vector has been reported, this is the first paper showing effective uptake of adenoviral vector by the EphA2R that is present on solid tumors.


Contact: Lai-Fu Li
World Journal of Gastroenterology

Related medicine news :

1. American Medical Association Clears Path for Adenoviral Conjunctivitis - Pink Eye - Detector
2. State Legislature Declares April 21 to 25, 2008 West Nile Virus and Mosquito and Vector Control Awareness Week
3. Non-Profit Healthcare Facilities Invited to Submit Essays in Vector180s Worthy Of Wi-Fi Contest
4. Vaporized viral vector shows promise in anti-cancer gene therapy
5. EaglePicher Technologies Introduces First Implantable Medical Cell Designed Specifically for Monitoring Applications
6. eDiets(R) Partners with alli(R) to Launch Specifically Designed Fresh Meal Delivery Program
7. Paro, the Worlds Only Robotic Baby Harp Seal - Designed Specifically for Therapy - to be Focus of Industry Event at Vinson Hall Retirement Community in McLean, Va., June 2
8. leViv Launches First Meal Programs Specifically Designed for Taste and Health
9. The First Treatment Specifically Approved for Huntingtons Disease Patients is Now Available in the United States
10. Video: Schering-Plough Introduces TINACTIN(R) CHILL, a Line of Antifungal Products Geared Specifically to Young Males
11. First and Only Weaning Product Based on 100% Non-Allergenic Amino-Acids Specifically Designed for Children With Cows Milk Protein Allergy and Multiple Food Protein Intolerance
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... Intellitec ... Dynamics SL User Group (MSDSLUG). Recognized as Microsoft’s official group for end users ... Dynamics SL software users, partners, industry experts and representatives. Intellitec Solutions’ membership status ...
(Date:11/27/2015)... ... November 27, 2015 , ... ... has prided itself for not only fulfilling the needs of advisers and clients ... an affordable price and providing top-tier customer service. However, there's always room for ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... CBD ... Accreditation of Allied Health Education Programs (CAAHEP) awarded accreditation to its Diagnostic Medical Sonography ... CAAHEP accredited colleges, as only one of twelve colleges and universities in the state ...
(Date:11/27/2015)... ... , ... Dr. Thomas Dunlap and Dr. Patrick Coleman , ... Emergency Medicine at St., Joseph Health System’s Santa Rosa Memorial Hospital , co-hosted ... similar ways and require time-critical intervention to avoid large area heart damage and progressive ...
(Date:11/27/2015)... ... 2015 , ... Indosoft Inc., developer and distributor of the ... LTS (Long Term Support) into its Q-Suite 5.10 product line. , Making the ... a version of Asterisk that will receive not only security fixes, but feature ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... WASHINGTON , Nov. 25, 2015  The ... Obstetricians and Gynecologists (ACOG), and the March of ... bipartisan Protecting Our Infants Act of 2015 ... the number of newborns born exposed to drugs, ... Since the bill,s introduction, all three organizations have ...
(Date:11/25/2015)... 2015 On Tuesday, November 24, 2015, ... against Wright Medical Technology, Inc. for product liability ... hip implant device, awarded $11 million in favor ... trial and three days of deliberations, the jury ... defectively designed and unreasonably dangerous, and that Wright ...
(Date:11/25/2015)... Kitov Pharma ceuticals ... biopharmaceutical company focused on the development of therapeutic candidates ... announced the closing of its previously announced underwritten public ... each representing 20 ordinary shares of the Company, and ... and warrants were issued in a fixed combination of ...
Breaking Medicine Technology: