Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.
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PMID:Enhancement of adenoviral transduction with polycationic liposomes in vivo. 1105 90

We have previously described oncolytic adenovirus (Ad) vectors KD3 and KD3-interferon (IFN) that were rendered cancer-specific by mutations in the E1A region of Ad; these mutations abolish binding of E1A proteins to p300/CBP and pRB. The antitumor activity of the vectors was enhanced by overexpression of the Adenovirus Death Protein (ADP, E3-11.6K) and by replication-linked expression of IFN-alpha. We hypothesized that the anticancer efficacy of the KD3-IFN vector could be further improved by expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). E1-deleted Ad vectors were constructed carrying reporter genes for enhanced green fluorescent protein or secreted placental alkaline phosphatase (SEAP) and a therapeutic gene for TRAIL under control of the TetON system. Expression of the genes was increased in the presence of a helper virus and the inducer doxycycline such that up to 231-fold activation of expression for the TetON-SEAP vector was obtained. Coinfection with TetON-TRAIL augmented oncolytic activity of KD3 and KD3-IFN in vitro. Induction of TRAIL expression did not reduce the yield of progeny virus. Combination of TetON-TRAIL and KD3-IFN produced superior antitumor activity in vivo as compared with either vector alone demonstrating the efficacy of a four-pronged cancer gene therapy approach, which includes Ad oncolysis, ADP overexpression, IFN-alpha-mediated immunotherapy, and pharmacologically controlled TRAIL activity.
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PMID:Anticancer activity of oncolytic adenovirus vector armed with IFN-alpha and ADP is enhanced by pharmacologically controlled expression of TRAIL. 1799