New strategy for the extension of the serum half-life of antibody fragments.
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| Abstract |
Antibody fragments can recognize their cognate antigen with high affinity and can be produced at high yields, but generally display rapid blood clearance profiles. For pharmaceutical applications, the serum half-life of antibody fragments is often extended by chemical modification with polymers or by genetic fusion to albumin or albumin-binding polypeptides. Here, we report that the site-specific chemical modification of a C-terminal cysteine residue in scFv antibody fragments with a small organic molecule capable of high-affinity binding to serum albumin substantially extends serum half-life in rodents. The strategy was implemented using the antibody fragment F8, specific to the alternatively spliced EDA domain of fibronectin, a tumor-associated antigen. The unmodified and chemically modified scFv-F8 antibody fragments were studied by biodistribution analysis in tumor-bearing mice, exhibiting a dramatic increase in tumor uptake for the albumin-binding antibody derivative. The data presented in this paper indicate that the chemical modification of the antibody fragment with the 2-(3-maleimidopropanamido)-6-(4-(4-iodophenyl)butanamido)hexanoate albumin-binding moiety may represent a general strategy for the extension of the serum half-life of antibody fragments and for the improvement of their in vivo targeting performance.
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| Authors | Sabrina Trüssel, Christoph Dumelin, Katharina Frey, Alessandra Villa, Fabian Buller, Dario Neri |
| Journal | Bioconjugate chemistry (Bioconjug Chem) Vol. 20 Issue 12 Pg. 2286-92 (Dec 2009) ISSN: 1520-4812 [Electronic] United States |
| PMID | 19916518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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