Targeting of LAK activity to CEA-expressing tumor cells with an anti-CEA scFv/IL-2 fusion protein

Background: Fusion of tumor-specific monoclonal antibody (MAb) and cytokine s has proved to be an efficient way to target cytokines to tumor cells and hence focuses the killing activity of effector cells to the target cells. W e previously produced a high affinity MAb, F11-39, against carcinoembryonic antigen (CEA), which is often overexpressed on the surface of various tumo r cells. Materials and Methods: To target the cytotoxicity of effector cell s to CEA-expressing tumor cells, we employed recombinant DNA techniques to fuse recombinant human interleukin-2 (rhIL-2) to a single chain variable fr agment (scFv) antibody derived from F11-39. The resulting fusion protein, d esignated F39scFv/IL-2, was expressed in the Sp2/0-Ag14 mouse hybridoma cel ls, purified by CFA-affinity chromatography and characterized for the CEA-b inding specificity and the IL-2 biological activity. Results: F39scFv/IL-2 protein effectively targeted rhIL-2 onto the surface of CEA-expressing tumo r cells and consequently introduced a specific cytotoxicity of lymphokine-a ctivated killer cells to the tumor cells. Conclusions: This approach may be used for in vivo administration to localize IL-2 to tumor tissues, maximiz ing the immune response to CEA-expressing tumors while keeping systemic sid e effects to a minimum.