Specific targeting strategies of cancer gene therapy using a single-chain variable fragment (scFv) with a high affinity for CEA.
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.
Kuroki
M
M
First Department of Biochemistry, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kurokima@fukuoka-u.ac.jp
Arakawa
F
F
Khare
P D
PD
Kuroki
M
M
Liao
S
S
Matsumoto
H
H
Abe
H
H
Imakiire
T
T
D000818:Animals; D000915:Antibody Affinity; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II