Antibody-toxin conjugation

The purpose of this chapter is to discuss our present knowledge concerning the numerous chemical means used to couple toxins to antibodies and to discuss how these methods influence the toxicity of the conjugate. The expanded interest in immunoconjugates is largely the result of two recent developments. The first development is that of monoclonal antibodies [1]. The advantages of monoclonals over serum-derived (polyclonal) antibodies are numerous: 1) specificity in binding to a single (chosen) antigen, 2) singularity in antibody class and thus control over features such as complement fixation, 3) generation of large quantities of the identical antibody and thus reproducibility between different laboratories and different times, and 4) since the immunoglobulin structure is constant, the chemical modification and separation techniques used to conjugate toxin should be both reproducible and more capable of generating a homogeneous product. In addition, the singular specificity and affinity permits meaningful biochemical studies, such as determination of affinity, receptor occupancy, and cellular antigen number, as well as biophysical characterization of the constructed immunotoxins (ITs).