A GUTLESS ADENOVIRAL VECTOR EXPRESSING FULL-LENGTH ANTI-Her2 ANTIBODY

被引:3
作者
Jiang, Ming-Hong [2 ]
Chen, Lin [1 ]
Li, Lin-Fang [2 ]
Wu, Hong-Ping [2 ]
Jiang, Li-Hua [2 ]
Qian, Yan-Zhen [2 ]
Fang, Guo-En [1 ]
Xue, Xu-Chao [1 ]
机构
[1] Second Mil Med Univ, Dept Gen Surg, Changhai Hosp, Shanghai 200438, Peoples R China
[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Viral & Gene, Shanghai 200438, Peoples R China
关键词
gene therapy; gutless adenovirus; monoclonal antibody; TERM TRANSGENE EXPRESSION; BREAST-CANCER; GENE-THERAPY; HEPATIC TRANSDUCTION; TRASTUZUMAB; OVEREXPRESSION; DISSEMINATION; PROSPECTS; LIVER;
D O I
10.1111/j.1440-1681.2009.05175.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
P>Therapeutic monoclonal antibodies are increasingly being used in clinical cancer treatment, but their complex technology and high cost limit their use. Helper-dependent (HD) adenoviruses are among the most efficient and safe gene therapy vectors capable of mediating long-term expression. Using Gateway (Invitrogen, San Diego, CA, USA) cloning technology, we constructed an HD-trastuzumab (TAb) plasmid carrying the full-length anti-HER2 antibody gene. Using an efficient recombinase, namely in vitro-evolved Flippase-expressing recombinase, to excise the helper virus packaging signal in producer cells, we developed a scalable HD vector production method. Antibody expression of HD-TAb in vitro was detected by ELISA and western blot. The full-length antibody gene delivery system allowed for continuous production of a full-length antibody at a high concentration. Bioactive antibody macromolecules were generated via gene transfer in vitro. In conclusion, HD adenoviral vectors can stably express a full-length antibody for prolonged periods without the difficulties associated with sophisticated antibody manufacture techniques and at a much lower cost. As a promising tool for gene therapy, this novel system can shorten the duration and reduce the expense of antibody development.
引用
收藏
页码:e26 / e31
页数:6
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