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 target antigens; they have been exploited in vivo for diagnostic and therapeutic applications as well. Recent advances in antibody engineering 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 locations inside mammalian cells, has provided a powerful new family of molecules for gene therapy applications. These intracellular antibodies are termed 'intrabodies'. Two clinical protocols have been approved by the RAC for the use of intrabodies in the treatment of an oncologic and an infectious disease. Their clinical use will in all likelihood become widespread if these initial studies show 'proof in principle'. In this article, the studies from laboratories that have used intrabodies 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.