Targeting strategy for gene delivery to carcinoembryonic antigen-producing cancer cells by retrovirus displaying a single-chain variable fragment antibody

被引:41
作者
Konishi, H
Ochiya, T
Chester, KA
Begent, RHJ
Muto, T
Sugimura, T
Terada, M
机构
[1] Natl Canc Ctr, Res Inst, Div Genet, Chuo Ku, Tokyo 104, Japan
[2] Univ Tokyo, Fac Med, Dept Surg 1, Tokyo 113, Japan
[3] Royal Free Hosp, Sch Med, Dept Clin Oncol, London NW1 4JL, England
关键词
D O I
10.1089/hum.1998.9.2-235
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy, Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach, Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies, Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for hepres simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells, These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.
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收藏
页码:235 / 248
页数:14
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