CHARACTERIZATION, RECEPTOR MAPPING AND BLOOD-BRAIN-BARRIER TRANSCYTOSIS OF ANTIBODIES TO THE HUMAN TRANSFERRIN RECEPTOR

Monoclonal antibodies to the human transferrin receptor were screened for binding to capillary vessels in human, monkey, rabbit and rat brai n tissue. Two antibodies were selected that bind both human and monkey but not rabbit or rat microvessels. With recombinant fragments of the human receptor, both antibodies were shown to bind to a region of the extracellular portion of the receptor that is relatively variable amo ng species, Binding, which was characterized by using purified recepto r and K562 cells, was not reduced by excess transferrin, indicating th at the antibodies bind the receptor at a site different from that of t ransferrin. When the antibodies were radiolabeled and injected i.v. in to cynomolgous monkeys, they distributed selectively to brain but not to other organs or tissues. The antibodies were found almost exclusive ly in the brain parenchyma, rather than the capillaries, indicating th at they had transcytosed the blood-brain barrier. These results show t hat antibodies to the human transferrin receptor cross the blood-brain barrier and may be useful for noninvasive delivery of therapeutic pro teins to the central nervous system.