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Antibodies 2012, 1(1), 2-18;

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 / Revised: 16 March 2012 / Accepted: 30 March 2012 / Published: 10 April 2012
(This article belongs to the Special Issue Bispecific Antibodies for Dual Targeting Strategies)
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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. View Full-Text
Keywords: dual-targeting; cancer therapy; effector cell; triplebody; NK-cell; macrophage; drug conjugates 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.

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