649. Increased Therapeutic Efficacy of the Prostate-Specific Oncolytic Adenovirus Ad[I/PPT-E1A] by Introduction of the Entire E3 Region or the Adenovirus Death Protein
التفاصيل البيبلوغرافية
العنوان:
649. Increased Therapeutic Efficacy of the Prostate-Specific Oncolytic Adenovirus Ad[I/PPT-E1A] by Introduction of the Entire E3 Region or the Adenovirus Death Protein
Conditionally replicating adenoviruses are developing as a complement to traditional cancer therapies. Ad[I/PPT-E1A] is a virus that replicates exclusively in prostate cells since the expression of E1A is controlled by the tissue specific promoter PPT. The regulatory PPT sequence is composed of a PSA enhancer, a PSMA enhancer and a TARP promoter. The H19 insulator (I) placed in front of PPT protects the regulatory sequence from interfering signals from the adenoviral backbone that otherwise can make the expression unspecific. This virus has now been improved by including only the active part of the H19 insulator and by adding either the entire adenoviral E3 region (Ad[iPPT-E1A, E3]) or just ADP (Ad[iPPT- E1A, ADP]). Since proteins expressed by the E3 region play a crucial role in blocking immune responses from the host, theseproteins are important for the persistence of the viral infection. ADP, which is located in the E3 region, is important for efficient viral release. These two viruses have been compared to Ad[I/PPT- E1A] and results from in vitro studies demonstrate a more efficient cell kill without altered specificity. The Ad[iPPT-E1A, E3] vector has also been evaluated in vivo by intratumoral injection of the virus in subcutaneous LNCaP tumors on nude mice. Treated mice showed tumor suppression compared to the control group. Ad[iPPT-E1A, E3] and Ad[iPPT-E1A, ADP] will be further investigated but so far both of them seem promising for use in the clinic.
