Abstract
In recent years, therapy with monoclonal antibodies has become standard of care in various clinical applications. Despite obvious clinical activity, not all patients respond and benefit from this generally well tolerated treatment option. Therefore, rational optimization of antibody therapy represents a major area of interest in translational research. Animal models and clinical data suggested important roles of Fc-mediated effector mechanisms such as antibody dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) in antibody therapy. These novel insights into the mechanisms of action mediated by monoclonal antibodies inspired the development of different engineering approaches to enhance/optimize antibodies' effector functions. Fc-engineering approaches by altering the Fc-bound glycosylation profile or by exchanging amino acids in the protein backbone have been intensively studied. Here, advanced and emerging technologies in Fc-engineering resulting in altered ADCC and CDC activity are summarized and experimental strategies to evaluate antibodies' effector functions are discussed.
| Original language | English |
|---|---|
| Journal | Methods |
| Volume | 65 |
| Issue number | 1 |
| Pages (from-to) | 105-113 |
| Number of pages | 9 |
| ISSN | 1046-2023 |
| DOIs | |
| Publication status | Published - 01.01.2014 |
Funding
Professor Dr. Christine Gaboriaud and Professor Dr. Gerard J. Arlaud are kindly acknowledged for providing the pdb coordinate files used to illustrate the putative IgG 1 /C1q interactions of CDC-optimized Fc variants. This work was supported by research grant 2007.065.2 from the Wilhelm Sander Stiftung (Neustadt, Germany) and a research grant DJCLS D 12/19 from the Deutsche José Carreras Leukämie Stiftung e.v. (Munich, Germany) . We apologize to all investigators whose important work in the field could not be cited because of space limitations.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
