Combination Gene Therapy with Conditionally Replicating Adenovirus (CRAD) and Adenovirus-Herpes Simplex Virus Thymidine Kinase (ad-HSTK) of Lung Cancer.

Analysis of adenovirus trans-complementation-mediated gene expression controlled by melanoma-specific TETP promoter in vitro

“…Strategies to improve experimental cancer therapy include co-delivery of RC oncolytic Ads together with RD vectors expressing therapeutic genes [ 17 , 21 , 22 , 26 , 28 , 30 , 31 , 33 - 39 ]. There is a large choice of candidate therapeutic genes that has been evaluated, including tumor-suppressor, immunomodulatory or cytotoxic genes.…”

“…Such a strong variation of trans-complementation-mediated enhancement has been found in other studies, and may depend on cell type used, exact transgene vector: CRAd ratio, time point of individual virus additions (variable in some studies), trans-activation of the CMV promoter by cellular and viral gene products [ 51 ], and most importantly, also the type and dynamic range of analysis system utilized for quantification. Enhancement values of > 50, e.g., were obtained by others when using luciferase assays [ 22 , 24 , 28 ], ELISA [ 38 , 39 ], and virus progeny titers [ 19 ] which have the largest dynamic range.…”

“…More recently, this system has led to new exciting applications for non-invasive in vivo imaging of tumor spread and assessment of Ad replication [ 24 - 27 ]. Therapeutic genes utilized in binary vector systems included prodrug converting enzymes such as herpes simplex virus-thymidine kinase [ 28 , 29 ] and P450 enzyme [ 21 ], suicide genes like Bcl-xs [ 30 ], p53 [ 31 , 32 ], p27 [ 25 ], tumor necrosis factor α-related apoptosis-inducing ligand [ 23 , 33 - 36 ], dominant-negative insulin-like growth factor-1R [ 22 ], antiangiogenic soluble vascular endothelial growth factor receptor 2-Fc [ 26 , 37 ], and immunostimulatory proteins like GM-CSF [ 33 , 38 ], IL-2 and IL-12 [ 39 ]. In most studies, co-administration of RD therapeutic vectors and CRAds was also tested in in vivo xenotransplant models.…”

“…In most studies, co-administration of RD therapeutic vectors and CRAds was also tested in in vivo xenotransplant models. Improved oncolytic efficacy was found and in some cases lead to complete and long lasting regression, which was not achieved when using the individual viral vectors alone [ 21 - 26 , 28 , 29 , 33 - 37 , 39 ].…”

Oncolytic Virotherapy Targeting Lung Cancer Drug Resistance

“…Lung cancer may also be an attractive target for OV Currant Opinion in Virology 2012, 2:629--635 therapy, partly because of the possibility of intranasal delivery of therapeutic viral particles [20]. The majority of OVs evaluated in preclinical models of NSCLC were adenoviruses [21][22][23], but therapeutic efficacy with other viruses such as herpes simplex virus [24], coxsackievirus [25], Newcastle disease virus [26], Seneca valley virus [27], reovirus [28,29] has also been reported. TG4010 is an OV-based anticancer vaccine, based on highly immunogenic, modified vaccinia virus vector expressing MUCl antigen, together with IL-2 as an immunoadjuvant to reverse suppression ofT-cell response [30].…”