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Fc engineering of antibodies and antibody derivatives by primary sequence alteration and their functional characterization.

Authors
  • Derer, Stefanie
  • Kellner, Christian
  • Rösner, Thies
  • Klausz, Katja
  • Glorius, Pia
  • Valerius, Thomas
  • Peipp, Matthias
Type
Published Article
Journal
Methods in Molecular Biology
Publication Date
Jan 01, 2014
Volume
1131
Pages
525–540
Identifiers
DOI: 10.1007/978-1-62703-992-5_33
PMID: 24515488
Source
Medline
License
Unknown

Abstract

Therapeutic antibodies used in the treatment of cancer patients are able to mediate diverse effector mechanisms. Dependent on tumor entity, localization, and tumor burden different effector mechanisms may contribute to the in vivo antitumor activity to a variable degree. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) have been suggested as being important for the in vivo activity of therapeutic antibodies like rituximab or trastuzumab. In recent years, several strategies have been pursued to further optimize the cytotoxic potential of monoclonal antibodies by modifying their Fc part (Fc engineering) with the ultimate goal to enhance antibody therapy.Since Fc engineering approaches are applicable to any Fc-containing molecule, strategies to enhance CDC or ADCC activity of full antibodies or scFv-Fc fusion proteins by altering the primary Fc sequence are described.

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