New strategy for the extension of the serum half-life of antibody fragments

Sabrina Trüssel, Christoph Dumelin, Katharina Frey, Alessandra Villa, Fabian Buller, Dario Neri

Research output: Contribution to journalArticle

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 albuminbinding 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.

Original languageEnglish
Pages (from-to)2286-2292
Number of pages7
JournalBioconjugate Chemistry
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 16 2009

Fingerprint

Immunoglobulin Fragments
Antibodies
Half-Life
Serum
Chemical modification
Tumors
Albumins
Single-Chain Antibodies
Antigens
Bearings (structural)
Neoplasm Antigens
Polypeptides
Fibronectins
Serum Albumin
Cysteine
Rodentia
Neoplasms
Polymers
Drug products
Blood

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Trüssel, S., Dumelin, C., Frey, K., Villa, A., Buller, F., & Neri, D. (2009). New strategy for the extension of the serum half-life of antibody fragments. Bioconjugate Chemistry, 20(12), 2286-2292. https://doi.org/10.1021/bc9002772

New strategy for the extension of the serum half-life of antibody fragments. / Trüssel, Sabrina; Dumelin, Christoph; Frey, Katharina; Villa, Alessandra; Buller, Fabian; Neri, Dario.

In: Bioconjugate Chemistry, Vol. 20, No. 12, 16.12.2009, p. 2286-2292.

Research output: Contribution to journalArticle

Trüssel, S, Dumelin, C, Frey, K, Villa, A, Buller, F & Neri, D 2009, 'New strategy for the extension of the serum half-life of antibody fragments', Bioconjugate Chemistry, vol. 20, no. 12, pp. 2286-2292. https://doi.org/10.1021/bc9002772
Trüssel S, Dumelin C, Frey K, Villa A, Buller F, Neri D. New strategy for the extension of the serum half-life of antibody fragments. Bioconjugate Chemistry. 2009 Dec 16;20(12):2286-2292. https://doi.org/10.1021/bc9002772
Trüssel, Sabrina ; Dumelin, Christoph ; Frey, Katharina ; Villa, Alessandra ; Buller, Fabian ; Neri, Dario. / New strategy for the extension of the serum half-life of antibody fragments. In: Bioconjugate Chemistry. 2009 ; Vol. 20, No. 12. pp. 2286-2292.
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