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 carcinoembry onic 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 ret rovector displaying anti-CEA single-chain variable fragment (scFv). We reco nstructed 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 m ethod is the specific redirecting of cytotoxic T-cells to CEA-expressing tu mor cells through chimeric receptors. We also reconstructed a chimeric rece ptor gene which encoded an anti-CEA scFv antibody and the zeta -chain of hu man 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 speci fic targeting of T-cells.