Abstract
In the present study, the receptor binding potential of transferrin (Tf) was linked to an antibody binding specificity. Human Tf was fused to mouse- human chimeric IgG3 at three positions: at the end of heavy chain constant region 1 (C(H)1), after the hinge, and after C(H)3. The resulting Tf-antibody fusion proteins were able to bind antigen and the Tf receptor. The C(H)3-Tf fusion protein showed no complement-mediated cytolysis but possessed IgG receptor I (FcγRI) binding activity. Most importantly, all of the fusion proteins demonstrated significant uptake into brain parenchyma, with 0.3% of the injected dose of the hinge-Tf fusion protein rapidly targeted to the brain. Recovery of iodinated C(H)3-Tf fusion protein from the brain parenchyma demonstrated that the fusion proteins can cross the blood-brain barrier intact. The binding specificity of these fusion proteins can be used for brain delivery of noncovalently bound ligands, such as drugs and peptides, or for targeting antigens present within the brain.
Original language | English (US) |
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Pages (from-to) | 2820-2824 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 92 |
Issue number | 7 |
DOIs | |
State | Published - Mar 28 1995 |
Externally published | Yes |
Keywords
- blood-brain barrier
- chimeric antibody
- growth factor receptors
- immunotherapy
ASJC Scopus subject areas
- Genetics
- General