TARGETING STRATEGY FOR GENE DELIVERY TO CARCINOEMBRYONIC ANTIGEN-PRODUCING CANCER-CELLS BY RETROVIRUS DISPLAYING A SINGLE-CHAIN VARIABLE FRAGMENT ANTIBODY

Cancer-specific antigens are promising targets for the specific delive ry of certain drugs or genes to cancer cells in cancer therapy, Carcin oembryonic antigen (CEA) is one of the cancer-associated antigens pred ominantly detected in the gastrointestinal cancer of the colon and sto mach, Targeting strategies for CEA-producing cancer cells have been th oroughly developed mainly by the production of monoclonal antibodies t o CEA and further single-chain variable fragment (scFv) antibodies, He re, 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 vi rus thymidine kinase (HSV-tk) or Escherichia coil beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, a nd specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of t he target cells, These results may have significant implications for t he use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vi vo cancer therapy.