Transferrin-antibody fusion proteins are effective in brain targeting

Seung Uon Shin, Phillip Friden, Marjorie Moran, Tracy Olson, Young Sook Kang, William M. Pardridge, Sherie L. Morrison

Research output: Contribution to journalArticle

80 Scopus citations

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 languageEnglish (US)
Pages (from-to)2820-2824
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number7
DOIs
StatePublished - Mar 28 1995

Keywords

  • blood-brain barrier
  • chimeric antibody
  • growth factor receptors
  • immunotherapy

ASJC Scopus subject areas

  • Genetics
  • General

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