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Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity
Department of Biology, University of Erlangen-Nuremberg, Erlangen 91058, Germany
Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH, Aachen 52074, Germany
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 28 February 2012; in revised form: 16 March 2012 / Accepted: 30 March 2012 / Published: 10 April 2012
Abstract: Here we review recombinant proteins with a capability for dual-targeting. These molecules address two different antigens on the same tumor cell and therefore are called “dual-targeting agents”. By virtue of binding a chosen pair of antigens on the malignant cell, preferential binding to antigen double-positive over single-positive cells can be achieved when both are present in the same environment. Therapeutic effects of such agents are based on different modes of action: (1) They can act as pro-apoptotic agents or by inhibiting pro-survival signals; (2) The dual recognition moiety can be fused to effector-domains, such as bacterial toxins or other drugs, leading to the generation of bispecific antibody-drug conjugates (ADCs); (3) Dual-targeting agents can further be used to redirect an effector-cell to the tumor. A new generation of scFv-derived fusion proteins are the tandem single chain triplebodies (sctbs), which carry two scFv binding sites for antigens on the tumor cell plus a third, specific for a trigger molecule on an effector cell. The ability of preferential or selective targeting of antigen double-positive over single-positive cells opens attractive new perspectives for the use of dual-targeting agents in cancer therapy, and possibly also for the treatment of certain inflammatory and autoimmune disorders.
Keywords: dual-targeting; cancer therapy; effector cell; triplebody; NK-cell; macrophage; drug conjugates
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Schubert, I.; Stein, C.; Fey, G.H. Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity. Antibodies 2012, 1, 2-18.
Schubert I, Stein C, Fey GH. Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity. Antibodies. 2012; 1(1):2-18.
Schubert, Ingo; Stein, Christoph; Fey, Georg H. 2012. "Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity." Antibodies 1, no. 1: 2-18.