title: AAV2-mediated gene transfer of VEGF-Trap with potent suppression of             primary breast tumor growth and spontaneous pulmonary metastases by long-term             expression.
abstract: Vascular endothelial growth factor (VEGF) is an important signaling protein             and a predominant mediator of angiogenesis in tumor growth and metastasis. Therefore,             antagonism of the VEGF pathway results in inhibition of abnormal angiogenesis,             then suppression of tumor growth and metastasis. VEGF-Trap, a high-affinity soluble             decoy receptor, is currently in phase II clinical trails, and has demonstrated             more efficacy in different types of solid tumors by intravenous injection every             two weeks. In our study, we used recombinant AAV2 as a delivery vehicle to achieve             long-lasting expression of VEGF Trap protein in a mouse model for the first time.             We report that AAV2-VEGF-Trap can be safely administered and sustained expression             in vivo via a single intravenously administration, simultaneously suppressing             primary tumor growth and preventing the pulmonary metastases of 4T1 tumors. Decreased             microvessel density and increased tumor cell apoptosis were observed in the treatment             group. AAV2-VEGF-Trap can obviously decrease not only the concentration of VEGF             in sera, but also the concentration of other angiogenic factors, such as aFGF,             bFGF, angiopoietin-1 and others. These studies suggest that AAV-mediated long-term             expression of VEGF-Trap is a useful and safe tool to block tumor progression and             inhibit spontaneous pulmonary metastases.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, PR China.
authors: Lian
authors: L
authors: Lu
authors: Shun-Tao
authors: ST
authors: Luo
authors: Hua Shan
authors: HS
authors: Shi
authors: Meng
authors: M
authors: Li
authors: Hai Long
authors: HL
authors: Zhang
authors: Sha Sha
authors: SS
authors: He
authors: Yan
authors: Y
authors: Liu
authors: Ying
authors: Y
authors: Pan
authors: Li
authors: L
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000235:genetics* / Q000517:prevention & control / Q000556:secondary / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D013939:Thymidine Phosphorylase; D040262:Receptors, Vascular Endothelial Growth Factor; C046366:angiogenin; D012259:Ribonuclease, Pancreatic