REDIRECTION OF T-CELL-MEDIATED CYTOTOXICITY BY A RECOMBINANT SINGLE-CHAIN FV MOLECULE

We have produced two single-chain Fv (sFv) proteins by bacterial perip lasmic secretion, one sFv with specificity for the hapten DNP, and the other for the human transferrin receptor. After solubilization and re folding, we recovered several mg of active sFv per liter of bacterial culture. Each sFv bound to cells bearing the appropriate Ag and could be used to direct targeted cellular cytotoxicity. Targeting relied on a universal bispecific antibody designed to cross-link CD3 on the cyto toxic T cell with a peptide fused to the sFv carboxyl-terminus. The un iversal bispecific antibody was used in combination with the Ag-specif ic sFv to redirect human cytotoxic T cells to kill a variety of target cells. Such an approach has a number of advantages that may make it u seful for the immunotherapy of cancer and other diseases.