INTRABODIES - TURNING THE HUMORAL IMMUNE-SYSTEM OUTSIDE IN FOR INTRACELLULAR IMMUNIZATION

Antibodies have long been used in biomedical science as in vitro tools for the identification, purification and functional manipulation of t arget antigens; they have been exploited in vivo for diagnostic and th erapeutic applications as well. Recent advances in antibody engineerin g have now Allowed the genes encoding antibodies to be manipulated so that the antigen binding domain can be expressed intracellularly. The specific and high-affinity binding properties of antibodies, combined with their ability to be stably expressed in precise intracellular loc ations inside mammalian cells, has provided a powerful new family of m olecules for gene therapy applications. These intracellular antibodies are termed 'intrabodies'. Two clinical protocols have been approved b y the RAC for the use of intrabodies bodies in the treatment of an onc ologic and an infectious disease. Their clinical use will in all likel ihood become widespread if these initial studies show 'proof in princi ple'. In this article, the studies from laboratories that have used in trabodies as molecular reagents for cancer therapy and for the control of infectious diseases will be reviewed and future directions of this technology will be discussed.