34 Expression of scFvs and scFv Fusion Proteins in Eukaryotic Cells

scFvs have considerable therapeutic potential against antigens (Ags) involved in disease processes (1 ,2) , either as proteins synthesized ex vivo for passive administration, or introduced by gene therapy for in vivo expression. Their small size confers many pharmacological advantages, compared to whole antibodies (Abs). However, they lack intrinsic biological activity because they lack the Fc (effector) portion of native (whole) Abs. Biological activity can be imparted to scFvs by generating bifunctional molecules, in which the scFv that specifically recognizes an Ag on the target cells is genetically fused to an effector molecule. Examples include cytokines (3 ,4 ) or prodrug-converting enzymes (1 ,5,6 ). Alternatively, the effector molecule can be a second scFv that retargets the molecules toward a cell population, e.g., for activation of cytotoxic T cells (7 ) or for gene therapy, e.g., targeting recombinant adenoviruses carrying therapeutic genes (8 ).