Prolonged in Vivo Residence Times of Antibody Fragments Associated with Albumin

Antibody fragments can be expressed at a high level in microbial systems, but they may have limited therapeutic value because they are rapidly eliminated from the body. We demonstrate here that site-specific conjugation or binding of bacterially derived Fab‘ to the long-lived protein serum albumin a...

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Bibliographic Details
Published in:	Bioconjugate chemistry Vol. 12; no. 5; pp. 750 - 756
Main Authors:	Smith, Bryan J, Popplewell, Andrew, Athwal, Dee, Chapman, Andrew P, Heywood, Sam, West, Shauna M, Carrington, Bruce, Nesbitt, Andrew, Lawson, Alastair D. G, Antoniw, Pari, Eddelston, Alison, Suitters, Amanda
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 01-09-2001
Subjects:	Animals Antibodies, Bacterial - chemistry Antibodies, Bispecific - administration & dosage Antibodies, Bispecific - chemistry Antibodies, Bispecific - pharmacokinetics Area Under Curve Cross-Linking Reagents - chemistry Half-Life Humans Immunoglobulin Fragments - administration & dosage Immunoglobulin Fragments - chemistry Immunoglobulin Variable Region - chemistry Immunoglobulin Variable Region - genetics Iodine Radioisotopes Male Rats Rats, Wistar Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - pharmacokinetics Serum Albumin - administration & dosage Serum Albumin - chemistry Serum Albumin - pharmacokinetics
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Summary:	Antibody fragments can be expressed at a high level in microbial systems, but they may have limited therapeutic value because they are rapidly eliminated from the body. We demonstrate here that site-specific conjugation or binding of bacterially derived Fab‘ to the long-lived protein serum albumin allows full retention of the antibody's binding characteristics while imparting the albumin's longevity in vivo. In rats the area under the curve for Fab‘ conjugated to rat serum albumin was 17-fold greater than for the control of Fab‘ conjugated to cysteine. Again, a bispecific F(ab‘)2 with specificity for rat serum albumin showed an area under the curve about 8-fold greater than did a F(ab‘)2 without specificity to albumin. Genetic fusions of scFv to albumin were similarly long-lived and could be expressed in yeast to provide the basis of a cost-effective production system.
Bibliography:	istex:FCAEC7C10265E9BB43161E4BE8FD5B87758F40B8 ark:/67375/TPS-854TGL9N-6 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1043-1802 1520-4812
DOI:	10.1021/bc010003g