Gene therapy using adenovirus-mediated full-length anti-HER-2 antibody for HER-2 overexpression cancers.
OBJECTIVE
Therapeutic monoclonal antibody is increasingly applied in many clinical applications, although complicated technologies and high cost still limit their wide applications. To obtain the sustained serum antibody concentration with one single injection and lower the cost of antibody protein therapy, an adenovirus-mediated full-length antibody gene therapy was developed.


METHODS
Full-length antibody light-chain and heavy-chain sequences were linked with internal ribosome entry site and constructed into adenoviral vector under the control of cytomegalovirus promoter. Antibody expression in vitro and in vivo were tested with ELISA, and its antitumor efficacy was evaluated in SKOV-3-inoculated nude mice.


RESULTS
Ad5-TAb-generated anti-HER-2 antibody presented the similar binding specificity with commercial trastuzumab. A single i.v. injection of 2 x 10(9) plaque-forming units of Ad5-TAb per mouse resulted in not only a sustained over 40 microg/mL serum antibody level for at least 4 weeks but also significant tumor elimination in the ovarian cancer SKOV-3-inoculated nude mice.


CONCLUSIONS
An in vivo full-length antibody gene delivery system allows continuous production of a full-length antibody at high concentration after a single administration. Bioactive antibody macromolecules can be generated via gene transfer in vivo. All the data suggest that this novel adenovirus-mediated antibody gene delivery can be used for the exploitation of antibodies, without being hampered by the sophisticated antibody manufacture techniques and high cost, and, furthermore, can shorten the duration and reduce the expense of antibody developments.
Jiang
Minghong
M
Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital, The Second Military Medical University, Shanghai, China.
Shi
Wenfang
W
Zhang
Qi
Q
Wang
Xinhua
X
Guo
Minggao
M
Cui
Zhenfu
Z
Su
Changqin
C
Yang
Qing
Q
Li
Yuemin
Y
Sham
Jonathan
J
Liu
Xinyuan
X
Wu
Mengchao
M
Qian
Qijun
Q
D000256:Adenoviridae; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002460:Cell Line; D045744:Cell Line, Tumor; D003587:Cytomegalovirus; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000627:therapeutic use*; D007147:Immunoglobulin Light Chains / Q000627:therapeutic use*; D007668:Kidney; D010051:Ovarian Neoplasms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014162:Transfection; D000068878:Trastuzumab; D010948:Viral Plaque Assay
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab