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Anticancer Res. 2000 Nov-Dec;20(6A):4067-71.

Specific targeting strategies of cancer gene therapy using a single-chain variable fragment (scFv) with a high affinity for CEA.

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1
First Department of Biochemistry, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kurokima@fukuoka-u.ac.jp

Abstract

Two specific targeting strategies of cancer gene therapy using carcinoembryonic antigen (CEA) as a target are briefly reviewed here. One method is the specific targeting of suicide genes to CEA-expressing tumor cells by a retrovector displaying anti-CEA single-chain variable fragment (scFv). We reconstructed a recombinant retroviral vector that displays both anti-CEA scFv-expressing chimeric and normal envelope proteins and carries the inducible nitric oxide synthase (iNOS) gene. This recombinant retrovirus specifically bound, infected and killed only CEA-expressing tumor cells, indicating the cell specific retroviral vector delivery of the iNOS gene. Another novel method is the specific redirecting of cytotoxic T-cells to CEA-expressing tumor cells through chimeric receptors. We also reconstructed a chimeric receptor gene which encoded an anti-CEA scFv antibody and the zeta-chain of human TCR/CD3 complex and expressed it on T-cell surface. When incubated with CEA-expressing tumor cells in vitro, the transduced T-cells tended to make a rosette-like formation around the tumor cells, suggesting the cell specific targeting of T-cells.

PMID:
11131674
[Indexed for MEDLINE]
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