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Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics

by Christoph Stein 1,†, Ingo Schubert 2,*,† and Georg H. Fey 2
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
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antibodies 2012, 1(1), 88-123;
Received: 19 April 2012 / Revised: 21 May 2012 / Accepted: 24 May 2012 / Published: 1 June 2012
(This article belongs to the Special Issue Modes of Antibody Action for Cancer Therapy)
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. View Full-Text
Keywords: NK-cell; T-cell; effector cell; tumor therapy; Fc receptor; bispecific antibody NK-cell; T-cell; effector cell; tumor therapy; Fc receptor; bispecific antibody
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Stein, C.; Schubert, I.; Fey, G.H. Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics. Antibodies 2012, 1, 88-123.

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