Application of Chemical Conjugation for the Preparation of Immunotoxins and Other Drug Conjugates for Targeting Therapeutics
Drug conjugates developed as a result of systemic pharmacotherapy are target-speciŠc cytotoxic agents.1 The underlying concept involves coupling a therapeutic agent to a delivery molecule with speciŠcity for a deŠned target-cell population. Antibodies with high afŠnity for antigens are natural choices for targeting agents.2-5 With the availability of high-afŠnity monoclonal antibodies (mAbs) and their fragments, the prospects of antibody-targeting therapeutics have become promising. Toxic substances that have been conjugated to mAbs include protein toxins, low-molecularweight drugs, biological response modiŠers, and radionuclides.6 Antibody-toxin conjugates are frequently termed immunotoxins, whereas immunoconjugates consisting of antibodies and lowmolecular-weight drugs such as methotrexate and adriamycin are called chemoimmunoconjugates. Immunomodulators contain biological response modiŠers that are known to have regulatory functions such as lymphokines, growth factors, and complement-activating cobra venom factor (CVF). Radioimmunoconjugates consist of radioactive isotopes, which may be used as therapeutics to kill cells with radiation or used for imaging.