Chapter 21 - Immunotoxin Conjugation Techniques

Abstract

Monoclonal antibodies directed against tumor antigens may be used as targeting agents for conducting certain cytotoxic substances to malignant cells for selective killing. Numerous cell-surface markers are known to proliferate in human solid tumor. The ability to raise monospecific antibodies to these markers creates the capacity to discretely target the tumor, causing cell death while leaving healthy cells alone. This chapter discusses the approach to constructing antibody immunoconjugates for cancer, which has taken a number of forms. One of the first designs used conjugates of monoclonal antibodies with toxins that were able to block protein synthesis at the ribosome level inside the cell. Other conjugate forms used radioactive labels that killed cells by over-exposure to radiation in proximity to where antibody docking occurred. Drug conjugates also were constructed that combined the known benefits of chemotherapy with the targeting capability of monoclonals. Conjugates of monoclonals with certain biological modulators such as lymphokines or growth factors were tried to affect malignant cell viability. Conjugates of monoclonal antibodies and protein toxins are undergoing extensive research for their usefulness in the treatment of cancer. Toxins of many different types can be used to create effective immunotoxin conjugates, including the proteins ricin from castor beans (Ricinus communis), abrin from Abrus precatorius, modeccin, gelonin from Gelonium multifl orum seeds, diphtheria toxin produced by Corynebacterium diphtheriae, pokeweed antiviral proteins from Phytolacca americana seeds, cobra venom factor (CVF), Pseudomonas exotoxin, restrictocin from Aspergillus Restrictus, momordin from Momordica Charantia seeds, saporin from Saponariaofficinalis seeds, as well as other ribosome-inactivating proteins (RIPs).