Targeting gene-virotherapy for cancer.
Gene therapy and viral therapy for cancer have therapeutic effects, but there has been no significant breakthrough in these two forms of therapy. Therefore, a new strategy called "targeting gene-virotherapy", which combines the advantages of gene therapy and viral therapy, has been formulated. This new therapy has stronger antitumor effects than either gene therapy or viral therapy. A tumor-specific replicative adenovirus vector ZD55 (E1B55KD deleted Adv.) was constructed and various single therapeutic genes were inserted into ZD55 to form ZD55-gene. These are the targeting gene-virotherapy genes. But experiments showed that a single gene was not effective in eliminating the tumor mass, and therefore two genes were separately inserted into ZD55. This strategy is called "targeting dual gene-virotherapy" (with PCT patent). Better results were obtained with this strategy, and all the xenograft tumor masses were completely eliminated in all mice when two suitable genes producing a synergetic or compensative effect were chosen. Twenty-six papers on these strategies have been published by researchers in our laboratory. Furthermore, an adenoviral vector with two targeting promoters harboring two antitumor genes has been constructed for cancer therapy. Promising results have been obtained with this adenoviral vector and another patent has been applied for. This antitumor strategy can be used to kill tumor cells completely with minimum damage to normal cells.
Liu
Xin-Yuan
XY
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. xyliu@sibs.ac.cn
Gu
Jing-Fa
JF
Shi
Wen-Fang
WF
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000627:therapeutic use; D051379:Mice; D024101:Mitochondrial Proteins / Q000627:therapeutic use; D009369:Neoplasms / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D014780:Viruses / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; C499605:Diablo protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011506:Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase