Marasco W A
Division of Human Retrovirology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Gene Ther. 1997 Jan;4(1):11-5. doi: 10.1038/sj.gt.3300346.
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.
长期以来，抗体在生物医学科学中一直被用作体外工具，用于识别、纯化和功能操纵靶抗原；它们也已被用于体内诊断和治疗应用。抗体工程的最新进展现在允许对编码抗体的基因进行操纵，以便抗原结合域能够在细胞内表达。抗体的特异性和高亲和力结合特性，以及它们在哺乳动物细胞内精确的细胞内位置稳定表达的能力，为基因治疗应用提供了一个强大的新分子家族。这些细胞内抗体被称为“内体抗体”。英国药品与保健品管理局（RAC）已批准两项临床试验方案，用于使用内体抗体治疗肿瘤和传染病。如果这些初步研究显示出“原理验证”，它们的临床应用很可能会广泛普及。在本文中，将对那些使用内体抗体作为癌症治疗和传染病控制分子试剂的实验室研究进行综述，并讨论该技术的未来发展方向。
