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Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics
Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH, Aachen 52074, Germany
Department of Biology, University of Erlangen-Nuremberg, Erlangen 91058, Germany
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 19 April 2012; in revised form: 21 May 2012 / Accepted: 24 May 2012 / Published: 1 June 2012
Abstract: Unmodified antibodies (abs) have been successful in the treatment of hematologic malignancies, but less so for the treatment of solid tumors. They trigger anti-tumor effects through their Fc-domains, and one way to improve their efficacy is to optimize their interaction with the effectors through Fc-engineering. Another way to empower abs is the design of bispecific abs and related fusion proteins allowing a narrower choice of effector cells. Here we review frequently chosen classes of effector cells, as well as common trigger molecules. Natural Killer (NK)- and T-cells are the most investigated populations in therapeutical approaches with bispecific agents until now. Catumaxomab, the first bispecific ab to receive drug approval, targets the tumor antigen Epithelial Cell Adhesion Molecule (EpCAM) and recruits T-cells via a binding site for the cell surface protein CD3. The next generation of recombinant ab-derivatives replaces the broadly reactive Fc-domain by a binding domain for a single selected trigger. Blinatumomab is the first clinically successful member of this class, targeting cancer cells via CD19 and engaging T-cells by CD3. Other investigators have developed related recombinant fusion proteins to recruit effectors, such as NK-cells and macrophages. The first such agents currently in preclinical and clinical development will be discussed.
Keywords: NK-cell; T-cell; effector cell; tumor therapy; Fc receptor; bispecific antibody
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MDPI and ACS Style
Stein, C.; Schubert, I.; Fey, G.H. Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics. Antibodies 2012, 1, 88-123.
Stein C, Schubert I, Fey GH. Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics. Antibodies. 2012; 1(1):88-123.
Stein, Christoph; Schubert, Ingo; Fey, Georg H. 2012. "Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics." Antibodies 1, no. 1: 88-123.