Antiangiogenesis gene armed tumor‐targeting adenovirus yields multiple antitumor activities in human HCC xenografts in nude mice

Abstract

The oncolytic virus with antiangiogenesis gene driven by the chimeric promoter has an improved killing efficacy on tumor cells, and may be useful for cancer gene therapy.

Adenovirus-Based Gene Therapy for Cancer

“…Previous studies confirmed the antitumor activity of various vectors carrying cytokine genes, such as interferons (Belardelli & Gresser, 1996), tumor necrosis factors (Zhang et al, 1996), drug-sensitive gene HSV-tk (Steele, 2000), antiangiogenesis genes (Fang et al, 2010). When these therapeutic genes were inserted into the genome of CRAds, they were selectively and highly expressed in cancer cells as a result of the cancer-selective replication of CARds, which further enhanced therapeutic effect targeting cancer cells without toxicity to normal tissues or cells.…”

“…The CRAd, AdSu-hE, in which a chimeric promoter of HER2 enhancer and hTERT promoter was used to drive the E1a gene, a cytomegalovirus promoter to control the human endostatin gene. In vivo intratumoral delivery of the CRAd to pre-established hepatocellular carcinoma tumors in nude mice induced a significant tumor reduction and, in some cases resulted in a complete tumor regression (Fang et al, 2010). Canstatin, a novel matrix-derived inhibitor of angiogenesis, was described as being at least 10-fold more active than endostatin (Kamphaus et al, 2000;Narazaki & Tosato, 2006).…”

“…These viruses are genetically modified to target, infect and replicate in cancer cells causing them to lyse with an improved, superior efficacy compared to non-replicating adenoviral vector which lacks the E1 genes. Here, combined with the studies of our group (Fang et al, 2009(Fang et al, , 2010He et al, 2009He et al, , 2010Hu et al, 2010;Ma et al, 2009;Su et al, 2004Su et al, , 2006aSu et al, , 2006bSu et al, , 2008aSu et al, , 2008b, we review the development of oncolytic adenovirus-based gene therapy for cancer, and figured the potential prospects of gene therapy in cancer treatment.…”

The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses

“…Many transgenes used to arm adenoviral vectors are designed to modify the tissue architecture. For instance, vectors that degrade the extracellular matrix, 6,7,33 inhibit the angiogenesis [34][35][36][37] or target the stromal cells 29 have been constructed. The CAM model is probably relevant to study such vectors.…”

An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells

“…This includes tumor-specific promoters which are used to drive the early viral gene, chimeric fibers which are constructed to improve infection efficacy, and viral genes which are deleted to prevent oncogene activation. The human telomerase reverse transcriptase promoter (TERTp) (5,6), hypoxia response elements (HRE)-containing promoter (7) and survivin promoter (8) are present in various cancer cells. Moreover, a human α-fetoprotein (AFP) promoter has also been used in AFP-producing cells (9,10) and a cyclooxygenase-2 (Cox2) promoter (11,12) used in cells overexpressing Cox2.…”