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A GUTLESS ADENOVIRAL VECTOR EXPRESSING FULL‐LENGTH ANTI‐Her2 ANTIBODY
Author(s) -
Jiang MingHong,
Chen Lin,
Li LinFang,
Wu HongPing,
Jiang LiHua,
Qian YanZhen,
Fang GuoEn,
Xue XuChao
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05175.x
Subject(s) - antibody , genetic enhancement , viral vector , monoclonal antibody , gene delivery , biology , transfection , microbiology and biotechnology , in vitro , virology , plasmid , transduction (biophysics) , recombinase , gene , recombinant dna , immunology , genetics , biochemistry , recombination
SUMMARY1 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. 2 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. 3 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 . 4 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.