Preparation and Preclinical Characterization of RNase-Based Immunofusion Proteins

Toxins from plants and bacteria have been coupled to antibodies to produce selective cytotoxic agents (immunotoxins) (1 –3 ). However, toxic side effects and immunogenicity have presented major obstacles to the successful clinical application of these proteins (4 –9 ). Production of humanized antibodies has alleviated the immunogenicity of the targeting component (10 ). Substituting plant and bacterial toxins with members of the pancreatic RNase A superfamily (for review see ref. 11 ) presents a solution to problems associated with the effector portion of immunotoxins (12 ).